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Hepatic Drug Metabolism and Aging

  • Drug Disposition
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Summary

Although there is considerable variation in the effect of age on drug biotransformation, the metabolism of many drugs is impaired in the elderly. Age-related physiological changes, such as a reduction in liver mass, hepatic metabolising enzyme activity, liver blood flow and alterations in plasma drug binding may account for the decreased elimination of some metabolised drugs in the elderly. It is difficult, however, to separate an effect of aging from a background of marked variation in the rate of metabolism due to factors such as individual metabolic phenotype, environmental influences, concomitant disease states and drug intake. The prevailing data suggest that initial doses of metabolised drugs should be reduced in older patients and then modified according to the clinical response. In most studies the elderly appear as responsive as young individuals to the effects of compounds which induce or inhibit the activity of cytochrome P450 isozymes. Concurrent use of other agents, which induce or inhibit drug metabolism, mandates dose adjustment as in younger patients.

Many questions remain unanswered. For instance, limitations of in vitro studies prevent any firm conclusion about changes in hepatic drug metabolising enzyme activity in the elderly. With aging, some pathways of drug metabolism may be selectively affected, but this has not been adequately scrutinised. The possibility that metabolism of stereoisomers may be altered in the elderly has not been adequately tested. The effect of aging on the distribution of polymorphic drug metabolism phenotypes is still not established, despite potential implications for disease susceptibility and survival advantage.

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References

  • Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. Journal of Cardiovascular Pharmacology 5: 1093–1096, 1983

    Article  PubMed  CAS  Google Scholar 

  • Abernethy DR, Greenblatt DJ, Shader RI. Imipramine and desipramine disposition in the elderly. Journal of Pharmacology and Experimental Therapeutics 232: 183–188, 1985

    PubMed  CAS  Google Scholar 

  • Abernethy DR, Kerzner L. Age effects on alpha-l-acid glycoprotein concentration and imipramine plasma protein binding. Journal of the American Geriatrics Society 32: 705–708, 1984

    PubMed  CAS  Google Scholar 

  • Abernethy DR, Schwartz JB, Plachetka JR, Todd EL, Egan JM. Comparison in young and elderly of pharmacodynamics and disposition of labetalol in systemic hypertension. American Journal of Cardiology 60: 697–702, 1987

    Article  PubMed  CAS  Google Scholar 

  • Abernethy DR, Schwartz JB, Todd EL, Luchi R, Snow E. Verapamil pharmacodynamics and disposition in young and elderly hypertensive patients. Annals of Internal Medicine 105: 329–336, 1986

    PubMed  CAS  Google Scholar 

  • Adebayo GI, Coker HAB. Cimetidine inhibition of theophylline elimination: the influence of adult age and the time course. Biopharmaceutics and Drug Disposition 8: 149–158, 1987

    Article  CAS  Google Scholar 

  • Adelman RC. Age-dependent effects in enzyme induction — a biochemical expression of aging. Experimental Gerontology 6: 75–87, 1971

    Article  PubMed  CAS  Google Scholar 

  • Advenier C, Gobert C, Harrison G, Bidet D, Richolet J, et al. Pharmacokinetic studies of rifampin in the elderly. Therapeutic Drug Monitoring 5: 61–65, 1983a

    Article  PubMed  CAS  Google Scholar 

  • Advenier C, Roux A, Gobert C, Massias P, Varoquaux O, et al. Pharmacokinetics of ketoprofen in the elderly. British Journal of Clinical Pharmacology 16: 65–70, 1983b

    Article  PubMed  CAS  Google Scholar 

  • Advenier C, Saint-Aubin A, Gobert C, Houin G, Albengres JP, et al. Pharmacokinetics of isoniazid in the elderly. British Journal of Clinical Pharmacology 10: 167–168, 1980

    Article  PubMed  CAS  Google Scholar 

  • Albert KS, Gillespie WR, Wagner JG, Pau A, Lockwood GF. Effects of age on the clinical pharmacokinetics of ibuprofen. American Journal of Medicine Ibuprofen Symposium; pp. 47–50, 1984

  • Allen MD, Greenblatt DJ, Harmatz JS, Shader RI. Desmethyl-diazepam kinetics in the elderly after oral prazepam. Clinical Pharmacology and Therapeutics 28: 196–202, 1980

    Article  PubMed  CAS  Google Scholar 

  • Antal EJ, Kramer PA, Mercik SA, Chapron DJ, Lawson IR. Theophylline pharmacokinetics in advanced age. British Journal of Clinical Pharmacology 12: 637–645, 1981

    Article  PubMed  CAS  Google Scholar 

  • Au WYW, Dutt AK, DeSoyza N. Theophylline kinetics in chronic obstructive airway disease in the elderly. Clinical Pharmacology and Therapeutics 37: 472–478, 1985

    Article  PubMed  CAS  Google Scholar 

  • Avram MJ, Fragen RJ, Caldwell NJ. Midazolam kinetics in women of two age groups. Clinical Pharmacology and Therapeutics 34: 505–508, 1983

    Article  PubMed  CAS  Google Scholar 

  • Bach B, Hansen JM, Kampmann JP, Rasmussen SN, Skovsted L. Disposition of antipyrine and phenytoin correlated with age and liver volume in man. Clinical Pharmacokinetics 6: 389–396, 1981

    Article  PubMed  CAS  Google Scholar 

  • Baillie SP, Bateman DN, Coates PE, Woodhouse KW. Age and the pharmacokinetics of morphine. Age and Ageing 18: 258–262, 1989

    Article  PubMed  CAS  Google Scholar 

  • Barbeau A, Roy M, Paris S, Cloutier T, Plasse L, et al. Ecogenetics of Parkinson’s disease: 4-hydroxylation of debrisoquine. Lancet 2: 1213–1216, 1985

    Article  PubMed  CAS  Google Scholar 

  • Barber HE, Hawksworth GM, Petrie JC, Rigby JW, Robb OJ, et al. Pharmacokinetics of atenolol and propranolol in young and elderly subjects. British Journal of Clinical Pharmacology 11: 118P–119P, 1981

    Google Scholar 

  • Bartsch W, Voight KD. Endocrine aspects of ageing in the male. Maturitas 6: 243–251, 1984

    Article  PubMed  CAS  Google Scholar 

  • Bauer LA, Davis R., Wilensky A, Raisys V, Levy RH. Valproic acid clearance: unbound fraction and diurnal variation in young and elderly adults. Clinical Pharmacology and Therapeutics 37: 697–700, 1985

    Article  PubMed  CAS  Google Scholar 

  • Bayer AJ, Pathy MSJ, Ankier SI. Pharmacokinetics and pharmacodynamic characteristics of trazodone in the elderly. British Journal of Clinical Pharmacology 16: 371–376, 1983

    Article  PubMed  CAS  Google Scholar 

  • Bayley N, Warne RW, Moulde RFW, Bury RW. A kinetic study of sulindac in the elderly. Australian and New Zealand Journal of Medicine 17: 39–42, 1987

    Article  PubMed  CAS  Google Scholar 

  • Bechtel WD, Goetake E. Elimination of brotizolam in elderly patients after multiple dose. European Journal of Clinical Pharmacology 31: 243–245, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bedjaoui A, Demontes-Mainard F, Raynal F, Vinçon G, Galley P, et al. Influence de l’âge et du sexe sur la pharmacocinétique du paracétamol. Thérapie 39: 353–359, 1984

    PubMed  CAS  Google Scholar 

  • Bendayan R, Pieper JA, Stewart RB, Caranasos GJ. Influence of age on serum protein binding of propranolol. European Journal of Clinical Pharmacology 26: 251–254, 1984

    Article  PubMed  CAS  Google Scholar 

  • Bentley JB, Borel JD, Nenad Jr RE, Gillespie TJ. Age and fentanyl pharmacokinetics. Anesthesia and Analgesia 61: 968–971, 1982

    Article  PubMed  CAS  Google Scholar 

  • Berkowitz BA, Ngai SH, Yang JC, Hempsted J, Spector S. The disposition of morphine in surgical patients. Clinical Pharmacology and Therapeutics 17: 629–635, 1975

    PubMed  CAS  Google Scholar 

  • Berlinger WG, Goldberg MJ, Spector R, Chiang CK, Ghoneim MM. Diphenhydramine: kinetics and psychomotor effects in elderly women. Clinical Pharmacology and Therapeutics 32: 387–391, 1982

    Article  PubMed  CAS  Google Scholar 

  • Birnbaum LS. Altered hepatic drug metabolism in senescent mice. Experimental Gerontology 15: 259–267, 1980

    Article  PubMed  CAS  Google Scholar 

  • Blanchard J. Protein binding of caffeine in young and elderly males. Journal of Pharmaceutical Sciences 71: 1415–1418, 1982

    Article  PubMed  CAS  Google Scholar 

  • Blanchard J, Sawers SJA. Comparative pharmacokinetics of caffeine in young and elderly men. Journal of Pharmacokinetics and Biopharmaceutics 11: 109–126, 1983

    Article  PubMed  CAS  Google Scholar 

  • Bonde J, Pedersen LE, Bødtker S, Angelo HR, Svensen TL, et al. The influence of age and smoking on the elimination of disopyramide. British Journal of Clinical Pharmacology 20: 453–458, 1985

    Article  PubMed  CAS  Google Scholar 

  • Boyd E. Normal variability in weight of the adult human liver and spleen. Archives of Pathology 16: 350–372, 1933

    Google Scholar 

  • Braithwaite R, Montgomery S, Dawling S. Age, depression and tricyclic antidepressant levels. In Crooks & Stevenson (Eds) Drugs and the elderly, pp. 133–144, University Park Press, Baltimore, 1979

    Google Scholar 

  • Brazzell RK, Rees MMC, Khoo KC, Szuma AJ, Sandor D, et al. Age and cibenzoline disposition. Clinical Pharmacology and Therapeutics 36: 613–619, 1984

    Article  PubMed  CAS  Google Scholar 

  • Briant RH, Dorrington RE, Cleal J, Williams FM. The rate of acetaminophen metabolism in the elderly and the young. Journal of the American Geriatrics Society 24: 359–361, 1976

    CAS  Google Scholar 

  • Briant RH, Dorrington RE, Ferry DG, Paxton JW. Bioavailability of metoprolol in young adults and the elderly, with additional studies on the effects of metoclopramide and probanthine. European Journal of Clinical Pharmacology 25: 353–356, 1983

    Article  PubMed  CAS  Google Scholar 

  • Briant RH, Liddle DE, Dorrington R, Williams FM. Plasma half-life of two analgesic drugs in young and elderly adults. New Zealand Medical Journal 82: 136–137, 1975

    Google Scholar 

  • Bryson SM, Verma N, Scott PJW, Rubin PC. Pharmacokinetics of valproic acid in young and elderly subjects. British Journal of Clinical Pharmacology 16: 104–105, 1983

    Article  PubMed  CAS  Google Scholar 

  • Buchanan WW, Grace EM. Pharmacokinetics of isoxicam in the elderly. American Journal of Medicine 79 (Suppl. 4B): 35–37, 1985

    Article  PubMed  CAS  Google Scholar 

  • Calloway NO, Foley CF, Lagerbloom P. Uncertainties in geriatric data: II. Organ size. Journal of the American Geriatrics Society 13: 20–28, 1965

    PubMed  CAS  Google Scholar 

  • Cammarata RJ, Rodnan GP, Fennell RM. Serum anti-gamma globulin and anti-nuclear factors in the aged. Journal of the American Medical Association 199: 115–118, 1967

    Article  Google Scholar 

  • Campbell AJ, Ferry DG, Edwards IR. Pharmacokinetic projections for isoxicam and piroxicam in old and young subjects. British Journal of Rheumatology 24: 176–178, 1985

    Article  PubMed  CAS  Google Scholar 

  • Campion EW, deLaby LO, Glynn RJ. The effect of age on serum albumin in healthy males: report from the Normative Aging Study. Journal of Gerontology 43: M18–M20, 1988

    Article  PubMed  CAS  Google Scholar 

  • Cartwright RA, Rogers HJ, Barnham-Hall D, Glasham RW, Ahmad RA, et al. Role of N-acetyltransferase phenotypes in bladder carcinogenesis: a pharmacogenetic epidemiological approach to bladder cancer. Lancer 2: 842–846, 1982

    Article  CAS  Google Scholar 

  • Castleden CM, George CF. The effect of ageing as the hepatic clearance of propranolol. British Journal of Clinical Pharmacology 7: 49–54, 1979

    Article  PubMed  CAS  Google Scholar 

  • Castleden CM, George CF, Marcer D, Hallett C. Increased sensitivity to nitrazepam in old age. British Medical Journal 1: 10–12, 1977

    Article  PubMed  CAS  Google Scholar 

  • Chan K, Kendall MJ, Mitchard M, Wells WDE, Vickers MD. The effect of ageing on plasma pethidine concentrations. British Journal of Clinical Pharmacology 2: 292–307, 1975

    Article  Google Scholar 

  • Chandler MHH, Scott SR, Blouin RA. Age-associated stereoselective alterations in hexobarbital metabolism. Clinical Pharmacology and Therapeutics 43: 436–441, 1988

    Article  PubMed  CAS  Google Scholar 

  • Christensen JH, Andreasen F, Jansen JA. Influence of age and sex on the pharmacokinetics of thiopentone. British Journal of Anaesthesia 53: 1189–1195, 1981

    Article  PubMed  CAS  Google Scholar 

  • Christensen JH, Andreasen F, Jansen JA. Thiopentone sensitivity in young and elderly women. British Journal of Anaesthesia 55: 33–40, 1983

    Article  PubMed  CAS  Google Scholar 

  • Cipolle RJ, Seifert RD, Neilan BA, Zaske DE, Hans F. Heparin kinetics: variables related to disposition and dosage. Clinical Pharmacology and Therapeutics 29: 387–393, 1981

    Article  PubMed  CAS  Google Scholar 

  • Cohen IA, Johnson CE, Berardi RR, Hyneck ML, Achem SR. Cimetidine-theophylline interaction: effects of age and cimetidine dose. Therapeutic Drug Monitoring 7: 426–434, 1985

    Article  PubMed  CAS  Google Scholar 

  • Collier PS, Kawar P, Gamble JAS, Dundee JW. Influence of age on pharmacokinetics of midazolam. Abstract. British Journal of Clinical Pharmacology 13: 602P, 1982

    Google Scholar 

  • Crossley K, Irvine P. Infectious diseases and immunization. In Cassell & Walsh (Eds) Geriatric medicine, 1st ed., pp. 311–331, Springer-Verlag, New York, 1984

    Google Scholar 

  • Crowley JJ, Cusack BJ, Jue SG, Koup KR, Park BK, et al. Aging and drug interactions: II. Effect of phenytoin and smoking on the oxidation of theophylline and cortisol in healthy men. Journal of Pharmacology and Experimental Therapeutics 245: 513–523, 1988

    PubMed  CAS  Google Scholar 

  • Cuny G, Royer RJ, Mur JM, Serot JM, Faure G, et al. Pharmacokinetics of salicylates in elderly. Gerontology 25: 49–55, 1979

    Article  PubMed  CAS  Google Scholar 

  • Cusack B. Drug metabolism in the elderly. Journal of Clinical Pharmacology 28: 571–576, 1988

    PubMed  CAS  Google Scholar 

  • Cusack B, Denham MJ. Nutritional status and drug disposition in the elderly. In Roe (Ed.) Drugs and nutrition in the geriatric patient, pp. 71–91, Churchill Livingstone, New York, 1984

    Google Scholar 

  • Cusack B, Kelly JG, Lavan J, Noel J, O’Malley K. Theophylline kinetics in relation to age: the importance of smoking. British Journal of Clinical Pharmacology 10: 109–114, 1980

    Article  PubMed  CAS  Google Scholar 

  • Cusack B, O’Malley K, Lavan J, Noel J, Kelly JG. Protein binding and disposition of lignocaine in the elderly. European Journal of Clinical Pharmacology 29: 323–329, 1985

    Article  PubMed  CAS  Google Scholar 

  • Cusson J, Nattel S, Matthews C, Talajic M, Laurand S. Age-dependent lidocaine disposition in patients with acute myocardial infarction. Clinical Pharmacology and Therapeutics 37: 381–386, 1985

    Article  PubMed  CAS  Google Scholar 

  • Darragh A, Gordon AJ, O’Byrne H, Hobbs D, Casey E. Singledose and steady-state pharmacokinetics of piroxicam in elderly vs young adults. European Journal of Clinical Pharmacology 28: 305–309, 1985

    Article  PubMed  CAS  Google Scholar 

  • Davidson JM, Chen JJ, Crapo L, Gray GD, Greenleaf WJ, et al. Hormonal changes and sexual functioning in aging men. Journal of Clinical Endocrinology and Metabolism 57: 71–77, 1983

    Article  PubMed  CAS  Google Scholar 

  • Dawling S, Crome P. Clinical pharmacokinetic considerations in the elderly: an update. Clinical Pharmacokinetics 17: 236–263, 1989

    Article  PubMed  CAS  Google Scholar 

  • Dawling S, Crome P, Braithwaite R. Pharmacokinetics of single oral doses of nortriptyline in depressed elderly hospital patients and young healthy volunteers. Clinical Pharmacokinetics 5: 394–401, 1980

    Article  PubMed  CAS  Google Scholar 

  • Dehlin O, Börnson G, Börjesson L, Abrahamsson L, Smith RB. Pharmacokinetics of triazolam in geriatric patients. European Journal of Clinical Pharmacology 25: 91–94, 1983

    Article  PubMed  CAS  Google Scholar 

  • Divoll M, Abernethy DR, Ameer B, Greenblatt DJ. Acetaminophen kinetics in the elderly. Clinical Pharmacology and Therapeutics 31: 141–156, 1982a

    Google Scholar 

  • Divoll M, Ameer B, Abernethy DR, Greenblatt DJ. Age does not alter acetaminophen absorption. Journal of the American Geriatrics Society 30: 240–244, 1982b

    PubMed  CAS  Google Scholar 

  • Divoll M, Greenblatt DJ, Abernethy DR, Shader RI. Cimetidine impairs clearance of antipyrine and desmethyldiazepam in the elderly. Journal of the American Geriatrics Society 30: 684–689, 1982c

    PubMed  CAS  Google Scholar 

  • Divoll M, Greenblatt DJ, Harmatz JS, Shader RI. Effect of age and gender on disposition of temazepam. Journal of Pharmaceutical Sciences 70: 1104–1107, 1981

    Article  PubMed  CAS  Google Scholar 

  • Divoll M, Greenblatt DJ, Ochs HR, Shader RI. Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex. Anesthesia and Analgesia 62: 1–8, 1983

    Article  PubMed  CAS  Google Scholar 

  • Donovan MA, Castleden CM, Pohl JEF, Kraft CA. The effect of age on digitoxin pharmacokinetics. British Journal of Clinical Pharmacology 11: 401–402, 1981

    Article  PubMed  CAS  Google Scholar 

  • Edwards DJ, Lalka D, Cerra F, Slaughter RL. Alpha-1-acid glycoprotein concentration and protein binding in trauma. Clinical Pharmacology and Therapeutics 32: 62–68, 1982

    Article  Google Scholar 

  • Eriksson LO, Wählin-Boll E, Odar-Cederlöf I, Lindholm L, Melander A. Influence of renal failure, rheumatoid arthritis and old age on the pharmacokinetics of diflunisal. European Journal of Clinical Pharmacology 36: 165–174, 1986

    Article  Google Scholar 

  • Evans DAP, Manley KA, McKusick VA. Genetic control of isoniazid metabolism in man. British Medical Journal 2: 485–491, 1960

    Article  PubMed  CAS  Google Scholar 

  • Farah JF, Taylor W, Rawlins MD, James O. Hepatic drug acetylation and oxidation: effects of ageing in man. British Medical Journal 2: 155–156, 1977

    Article  PubMed  CAS  Google Scholar 

  • Feely J, Pareira L, Guy E, Hockings N. Factors affecting the response to inhibition of drug metabolism by cimetidine — dose response and sensitivity of elderly and induced subjects. British Journal of Clinical Pharmacology 17: 77–81, 1984

    Article  PubMed  CAS  Google Scholar 

  • Flanagan RJ, Johnston A, White AST, Crome P. Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage. British Journal of Clinical Pharmacology 28: 463–469, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fox RW, Samaan S, Bukantz SC, Lockey RF. Theophylline kinetics in a geriatric group. Clinical Pharmacology and Therapeutics 34: 60–67, 1983

    Article  PubMed  CAS  Google Scholar 

  • Friedman H, Greenblatt DJ, Scavone JM, Burstein ES, Ochs HR, et al. Clearance of the antihistamine doxylamine reduced in elderly men but not in elderly women. Clinical Pharmacokinetics 16: 312–316, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fulton B, James O, Rawlins MD. The influence of age on the pharmacokinetics of paracetamol. Abstract. British Journal of Clinical Pharmacology 7: 418P, 1979

    Google Scholar 

  • Gachály B, Vas A, Hajós P, Káldor A. Acetylator phenotypes: effects of age. European Journal of Clinical Pharmacology 26: 43–45, 1984

    Article  Google Scholar 

  • Gachály B, Vas A, Káldor A. Ageing and acetylator phenotype (letter). European Journal of Clinical Pharmacology 29: 377–378, 1985

    Article  Google Scholar 

  • Geokas MC, Haverback BJ. The aging gastrointestinal tract. American Journal of Surgery 117: 881–892, 1969

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ. Reduced serum albumin concentration in the elderly: a report from the Boston Surveillance Program. Journal of the American Geriatrics Society 27: 20–22, 1979

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Boxenbaum HG, Matlis R, Ochs H, et al. Influence of age, gender, and obesity on salicylate kinetics following single doses of aspirin. Arthritis and Rheumatism 29: 971–980, 1986

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Locniskar A, Ochs HR, Harmatz JS, et al. Age, sex, and nitrazepam kinetics: relation to antipyrine disposition. Clinical Pharmacology and Therapeutics 38: 697–703, 1985a

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Matlis R, Harmatz JS, Shader RI. Absorption and disposition of ibuprofen in the elderly. Arthritis and Rheumatism 27: 1066–1069, 1984

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Allen MD, Harmatz JS, Shader RI. Diazepam disposition determinants. Clinical Pharmacology and Therapeutics 27: 301–312, 1980a

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Allen MD, Locniskar A, Harmatz JS, Shader RI. Lorazepam kinetics in the elderly. Clinical Pharmacology and Therapeutics 26: 103–113, 1979

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Abernethy DR, Harmatz JS, Shader RI. Antipyrine kinetics in the elderly: prediction of age-related changes in benzodiazepine oxidizing capacity. Journal of Pharmacology and Experimental Therapeutics 220: 120–126, 1982a

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB. et al. Alprazolam kinetics in the elderly: relation to antipyrine disposition. Archives of General Psychiatry 40: 287–290, 1983a

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, et al. Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity. British Journal of Clinical Pharmacology 15: 303–309, 1983b

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Harmatz JS, MacLaughlin DS, Shader RI. Kinetics and clinical effects of flurazepam in young and elderly noninsomniacs. Clinical Pharmacology and Therapeutics 30: 475–486, 1981a

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Oxazepam kinetics: effects of age and sex. Journal of Pharmacology and Experimental Therapeutics 215: 86–91, 1980b

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll MK, Harmatz JS, Shader RI. Antipyrine absorption and disposition in the elderly. Pharmacology 36: 125–133, 1988

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, et al. Clobazam kinetics in the elderly. British Journal of Clinical Pharmacology 12: 631–636, 1981b

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, et al. Reduced single-dose clearance of clobazem in elderly men predicts increased multiple-dose accumulation. Clinical Pharmacokinetics 8: 83–94, 1983c

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Friedman H, Burnstein ES, Scavone JM, Blyden GT, et al. Trazodone kinetics: effects of age, gender, and obesity. Clinical Pharmacology and Therapeutics 42: 193–200, 1987

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Matlis R, Scavone JM, Blyden GT, Harmatz JS, et al. Oxaprozin pharmacokinetics in the elderly. British Journal of Clinical Pharmacology 19: 373–378, 1985b

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Sellers EM, Shader RI. Drug disposition in old age. New England Journal of Medicine 306: 1081–1088, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Gretzer I, Alván G, Dunér H, Garle M, Sjöqvist F. Beta-blocking effect and pharmacokinetics of pindolol in young and elderly hypotensive patients. European Journal of Clinical Pharmacology 31: 415–418, 1986

    Article  PubMed  CAS  Google Scholar 

  • Guengerich FP, Distlerath LM, Reilly PEB, Wolff T, Shimada T, et al. Human-liver cytochromes P-450 involved in polymorphisms of drug oxidation. Xenobiotica 16: 367–378, 1986

    Article  PubMed  CAS  Google Scholar 

  • Hamdy RC, Murnane B, Perera N, Woodcock K, Koch IM. The pharmacokinetics of benoxaprofen in elderly subjects. European Journal of Rheumatology and Inflammation 5: 69–75, 1982

    PubMed  CAS  Google Scholar 

  • Harten J, Burggraaf J, Ligthart G, Brummelen P, Breimer DD. Single- and multiple-dose nisoldipine kinetics and effects in the young, the middle-aged, and the elderly. Clinical Pharmacology and Therapeutics 45: 600–607, 1989

    Article  PubMed  Google Scholar 

  • Hayes MJ, Langman MJS, Short AH. Changes in drug metabolism with increasing age: 2. Phenytoin clearance and protein binding. British Journal of Clinical Pharmacology 2: 73–79, 1975

    PubMed  CAS  Google Scholar 

  • Hayes MJ, Sprackling M, Langman MJS. Changes in the plasma clearance and protein binding of carbenoxolone with age, and their possible relationship with adverse drug effects. Gut 18: 1054–1058, 1977

    Article  PubMed  CAS  Google Scholar 

  • Helmers H, Peer AV, Woestenborghs R, Noorduin H, Heykants J. Alfentanil kinetics in the elderly. Clinical Pharmacology and Therapeutics 36: 239–243, 1984

    Article  PubMed  CAS  Google Scholar 

  • Herman RJ, Biolliaz J, Shaheen O, Wood AJJ, Wilkinson GR. Induction of propranolol metabolism by rifampin in the elderly (Abstract 274). Abstract I. p. 102, III World Conference on Clinical Pharmacology and Therapeutics. Stockholm. Sweden. 1986

  • Herman RJ, McAllister CB, Branch RA, Wilkinson GR. Effects of age on meperidine disposition. Clinical Pharmacology and Therapeutics 37: 19–24, 1985

    Article  PubMed  CAS  Google Scholar 

  • Hilbert JM. Chung M, Radwanski E, Gural R, Symchowicz S, et al. Quazepam kinetics in the elderly. Clinical Pharmacology and Therapeutics 36: 566–569, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ho PC, Triggs EJ, Bourne DWA, Heazlewood VJ. The effects of age and sex on the disposition of acetylsalicylic acid and its metabolites. British Journal of Clinical Pharmacology 19: 675–684, 1985

    Article  PubMed  CAS  Google Scholar 

  • Hockings N, Pall A, Moody J, Davidson AVM, Davidson DLW. Effects of age on meperidine disposition. British Journal of Clinical Pharmacology 22: 725–728, 1986

    Article  PubMed  CAS  Google Scholar 

  • Holmberg L, Odar-Cedcrlöf I, Boréus LO, Heyner L, Ehrnebo M. Comparative disposition of pethidine and norpethidine in old and young patients. European Journal of Clinical Pharmacology 22: 175–179, 1982

    Article  PubMed  CAS  Google Scholar 

  • Homeida M, Robert CJC, Halliwell M, Read AE, Branch RA. Antipyrine clearance per unit volume liver: an assessment of hepatic function in chronic liver disease. Gut 20: 596–601, 1979

    Article  PubMed  CAS  Google Scholar 

  • Hotraphinyo K, Triggs EJ, Maybloom B, Maclaine-Cross A. Warfarin sodium: steady state plasma levels and patient age. Clinical and Experimental Pharmacology and Therapeutics 5: 143–149, 1978

    CAS  Google Scholar 

  • Hulme A, MacLennan WJ, Ritchie RT, John VA, Shotton PA. Baclofen in the elderly stroke patient; its side-effects and pharmacokinetics. European Journal of Clinical Pharmacology 29: 467–469, 1985

    Article  PubMed  CAS  Google Scholar 

  • Humpel M, Nieuweboer B, Milius W, Hanke H, Wendt H. Kinetics and biotransformation of lormetazepam: II. Radioimmunologic determinations in plasma and urine of young and elderly subjects: first-pass effect. Clinical Pharmacology and Therapeutics 28: 673–679, 1980

    Article  PubMed  CAS  Google Scholar 

  • Iselius L, Evans DAP. Formal genetics of isoniazid metabolism in man. Clinical Pharmacokinetics 8: 541–566, 1983

    Article  PubMed  CAS  Google Scholar 

  • Ishizaki T, Hirayama H, Tawara K, Nakaya H, Sato M, et al. Pharmacokinetics and pharmacodynamics in young normal and elderly hypertensive subjects: a study using sotalol as a model drug. Journal of Pharmacology and Experimental Therapeutics 212: 173–181, 1980

    PubMed  CAS  Google Scholar 

  • Jackson SHD, Johnston A, Woollard R, Turner P. The relationship between theophylline clearance and age in adult life. European Journal of Clinical Pharmacology 36: 29–34, 1989

    Article  PubMed  CAS  Google Scholar 

  • Jaillon P, Gardin ME, Lecocq B, Richard MO, Meignan W, et al. Pharmacokinetics of nalbuphine in infants, young healthy volunteers, and elderly patients. Clinical Pharmacology and Therapeutics 46: 226–233, 1989

    Article  PubMed  CAS  Google Scholar 

  • Jori A, DiSalle E, Quadri A. Rate of aminopyrine disappearance from plasma in young and aged humans. Pharmacology 11: 273–279, 1972

    Article  Google Scholar 

  • Jochemsen R, Nandi KL, Corless D, Wesselman JGJ, Breimer DD. Pharmcokinetics of brotizolam in the elderly. British Journal of Clinical Pharmacology 16: 299S–307S, 1983

    Article  PubMed  Google Scholar 

  • Jung D, Mayersohn M, Perrier D, Calkins J, Saunders R. Thiopental disposition as a function of age in female patients undergoing surgery. Anesthesiology 56: 263–268, 1982

    Article  PubMed  CAS  Google Scholar 

  • Jusko WJ. Role of tobacco smoking in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 6: 7–39, 1978

    Article  PubMed  CAS  Google Scholar 

  • Jusko WJ, Gardner MJ, Mangione A, Schentag J, Koup J, et al. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. Journal of Pharmacetuical Sciences 86: 1358–1365, 1979

    Article  Google Scholar 

  • Jusko WJ, Koup JR, Vance JW, Schentag JJ, Kuntzky P. Intravenous theophylline therapy: nomogram guidelines. Annals of Internal Medicine 86: 400–404, 1977

    PubMed  CAS  Google Scholar 

  • Kalow W. Genetics of drug transformation. Clinical Biochemistry 19: 76–82, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kalow W. Genetic variation in the human hepatic cytochrome P-450 system. European Journal of Clinical Pharmacology 31: 633–641, 1987

    Article  PubMed  CAS  Google Scholar 

  • Kamataki T, Maeda K, Shimada M, Kitani K, Nagai T, et al. Age-related alterations in the activities of drug metabolizing enzymes and contents of sex-specific forms of cytochrome P-450 in liver microsomes from male and female rats. Journal of Pharmacology and Experimental Therapeutics 233: 222–228, 1985

    PubMed  CAS  Google Scholar 

  • Kampmann JP, Mortensen HB, Bach B, Waldorff S, Kristensen MB, et al. Kinetics of propylthiouracil in elderly. Acta Medica Scandinavica 624 (Suppl.): 93–98, 1979

    PubMed  CAS  Google Scholar 

  • Kangas L, Iisalo E, Kanto J, Lehtinen B, Pynnönen S, et al. Human pharmacokinetics of nitrazepam: effect of age and diseases. European Journal of Clinical Pharmacology 15: 163–170, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kanto J, Aaltonen L, Himberg JJ, Hovi-Viander M. Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study. Anesthesia and Analgesia 65: 15–20, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kanto J, Kangas L, Aaltonen L, Hilke H. Effects of age on the pharmacokinetics and sedative effect of flunitrazepam. International Journal of Clinical Pharmacology Therapeutics and Toxicology 19: 400–404, 1981

    CAS  Google Scholar 

  • Kanto J, Mäenpää M, Mäntylä R, Sellman R, Valovirta E. Effect of age on the pharmacokinetics of diazepam given in conjunction with spinal anesthesia. Anesthesiology 51: 154–159, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kanto J, Sjövall S, Erkkola R, Himberg JJ, Kangas L. Placental transfer and maternal midazolam kinetics. Clinical Pharmacology and Therapeutics 33: 786–791, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kato R, Takanaka A. Metabolism of drugs in old rats: I. Activities of NADPH-linked electron transport and drug-metabolizing enzyme system in liver microsomes in old rats. Japanese Journal of Pharmacology 18: 389–396, 1968a

    Article  PubMed  CAS  Google Scholar 

  • Kato R, Takanaka A. Metabolism of drugs in old rats: II. Metabolism in vivo and effects of drugs in old rats. Japanese Journal of Pharmacology 18: 389–396, 1968b

    Article  PubMed  CAS  Google Scholar 

  • Kato R, Vassanelli P, Frontino G, Chiesara E. Variation in the activity of liver microsomal drug-metabolizing enzymes in rats in relation to age. Biochemical Pharmacology 13: 1037–1051, 1964

    Article  PubMed  CAS  Google Scholar 

  • Kelly JG, McGarry K, O’Malley K, O’Brien ET. Bioavailability of labetalol increases with age. British Journal of Clinical Pharmacology 14: 304–305, 1982

    Article  PubMed  CAS  Google Scholar 

  • Kendall MJ. Pharmacokinetics of oxprenolol in the elderly. American Journal of Cardiology 52: 54D–56D, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kendall MJ, Chellingsworth MC, Jubb R, Thawley AR, Undre NA, et al. Pharmacokinetic study of the active metabolite of nabumethone in young healthy subjects and older arthritis patients. European Journal of Clinical Pharmacology 36: 299–305, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kenney RA. Physiology of aging. In Geokas (Ed.) The aging process, Clinics in Geriatric Medicine, Vol. I, pp. 37–59, 1985

  • Kergueris MF, Bourin M, Larousse C. Pharmacokinetics of isoniazid: influence of age. European Journal of Clinical Pharmacology 30: 335–340, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kirkpatnck T, Cockshott ID, Douglas EJ, Nimmo WS. Pharmacokinetics of propofol (diprivan) in elderly patients. British Journal of Anaesthesia 60: 146–150, 1988

    Article  Google Scholar 

  • Kitani K. Drugs and ageing liver — a critical reevaluation of rodent studies. In Van Bezooijen (Ed.) Pharmacological, morphological and physiological aspects of liver ageing, Vol. 1, pp. 105–114, EURAGE, The Netherlands, 1984

    Google Scholar 

  • Kjtani K, Kanai S, Miura P, Morita Y, Kisahara M. The effect of aging on the biliary excretion of ouabain in the rat. Experimental Gerontology 13: 9–17, 1978

    Article  Google Scholar 

  • Klem J, Murray GR, Laake K. Pharmacokinetics of temazepam in geriatric patients. European Journal of Clinical Pharmacology 30: 745–747, 1986

    Article  PubMed  CAS  Google Scholar 

  • Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. Journal of Clinical Investigation 55: 347–359, 1975

    Article  PubMed  CAS  Google Scholar 

  • Klotz U, Müller-Seydlitz P. Altered elimination of desmethyldiazepam in the elderly. British Journal of Clinical Pharmacology 7: 119–120, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, et al. Effects of aging and liver disease on disposition of lorazepam. Clinical Pharmacology and Therapeutics 24: 411–419, 1978

    PubMed  CAS  Google Scholar 

  • Larsson M, Landahl S, Lundborg P, Regårdh CG. Pharmacokinetics of metoprolol in healthy, elderly, non-smoking individuals after single dose and two weeks treatment. European Journal of Clinical Pharmacology 27: 217–222, 1984

    Article  PubMed  CAS  Google Scholar 

  • Lavène D, Humbert H, Kiechel JR, Ducreuzed C, Lajoie D, et al. Hydergine pharmacokinetics in the elderly. Journal of Pharmacology 16 (Suppl. III): 135–143, 1985

    Google Scholar 

  • Lehmann AB. Review: undernutrition in elderly people. Age and Ageing 18: 339–353, 1989

    Article  PubMed  CAS  Google Scholar 

  • Liddell DE, Williams FM, Briant RH. Phenazone (antipyrine) metabolism and distribution in young and elderly adults. Clinical and Experimental Pharmacology and Physiology 2: 481–487, 1975

    Article  PubMed  CAS  Google Scholar 

  • Loi C-M, Vestal RE. Drug metabolism in the elderly. Pharmacology and Therapeutics 36: 131–149, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ludwig E, Csiba A, Magyar T, Szöcs G, Graber H. Age-associated pharmacokinetic changes of metronidazole. International Journal of Clinical Pharmacology Therapeutics and Toxicology 21: 87–91, 1983

    CAS  Google Scholar 

  • Lund B, Egsmose C, Knudsen O, Andersen RB. Pharmacokinetic profile of indoprofen in elderly subjects. British Journal of Clinical Pharmacology 22: 721–724, 1986

    Article  PubMed  CAS  Google Scholar 

  • Lunell E, Borgå O. Pharmacokinetics of enprofylline in healthy elderly subjects. European Journal of Clinical Pharmacology 32: 67–70, 1987

    Article  PubMed  CAS  Google Scholar 

  • Macklon AF, Barton M, James O, Rawlins MD. The effect of age on the pharmacokinetics of diazepam. Clinical Science 59: 479–483, 1980

    PubMed  CAS  Google Scholar 

  • Macleod SM, Giles HG, Bengert B, Liu FF, Sellers EM. Age- and gender-related differences in diazepam pharmacokinetics. Journal of Clinical Pharmacology 19: 15–19, 1979

    PubMed  CAS  Google Scholar 

  • Maguire KP, Burrows GD, Norman RT, Scoffins BA. Metabolism and pharmacokinetics of dothiepin. British Journal of Clinical Pharmacology 12: 405–409, 1981

    Article  PubMed  CAS  Google Scholar 

  • Maguire KP, Norman TR, McIntyre I, Burrows GD. Clinical pharmacokinetics of dothiepin: single-dose kinetics in patients and prediction of steady-state concentrations. Clinical Pharmacokinetics 8: 179–185, 1983

    Article  PubMed  CAS  Google Scholar 

  • Maloney AG, Schmucker DL, Vessey DS, Wang RK. The effects of ageing on the hepatic microsomal mixed-function oxidase system of male and female monkeys. Hepatology 6: 282–287, 1986

    Article  PubMed  CAS  Google Scholar 

  • Marchesini G, Bua V, Brunori A, Bianchi G, Pisi P, et al. Galactose elimination capacity and liver volume in ageing man. Hepatology 8: 1079–1083, 1988

    Article  PubMed  CAS  Google Scholar 

  • Mattila J, Mantyla R, Lamminsivu U, Mannisto P. Pharmacokinetics of graded oral doses of sulindac in man. Arzneimittel-Forschung 34: 226–229, 1984

    PubMed  CAS  Google Scholar 

  • McVerry RM, Lethbridge J, Martin N, Mukerjee SK, Littler T, et al. Pharmacokinetics of naproxen in elderly patients. European Journal of Clinical Pharmacology 31: 463–468, 1986

    Article  PubMed  CAS  Google Scholar 

  • Melander A, Bodin NO, Danielson K, Gustafson B, Haglund B, et al. Absorption and elimination of d-propoxyphene, acetyl-salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects. Acta Medica Scandinavica 203: 121–124, 1978

    Article  PubMed  CAS  Google Scholar 

  • Miners JO, Penhall R, Robson RA, Birkett DJ. Comparison of paracetamol metabolism in young adult and elderly males. European Journal of Clinical Pharmacology 35: 157–160, 1988

    Article  PubMed  CAS  Google Scholar 

  • Miskolczi P, Vereczkey L, Szalay L, Göndöcs C. Effect of age on the pharmacokinetics of vinpocetine (Cavinton) and apovincaminic acid. European Journal of Clinical Pharmacology 33: 185–189, 1987

    Article  PubMed  CAS  Google Scholar 

  • Moltz KH, Gielsdorf W, Rasper J, Jaeger H, Hausleiter HJ, et al. Comparison of the pharmacokinetic profile of metaclazepam in old and young volunteers. European Journal of Clinical Pharmacology 29: 247–249, 1985

    Article  Google Scholar 

  • Montamat SC, Abernethy DR. Calcium antagonists in geriatric patients: diltiazem in elderly persons with hypertension. Clinical Pharmacology and Therapeutics 45: 682–691, 1989

    Article  PubMed  CAS  Google Scholar 

  • Montgomery PR, Berger LG, Mitenko PA, Sitar DS. Salicylate metabolism: effects of age and sex in adults. Clinical Pharmacology and Therapeutics 39: 571–576, 1986

    Article  PubMed  CAS  Google Scholar 

  • Mucklow JC, Fräser HS. The effects of age and smoking upon antipyrine metabolism. British Journal of Clinical Pharmacology 9: 612–614, 1980

    Article  Google Scholar 

  • Murray GR, Franklin RA, Graham DF, Lewis RR, Bolland ME. Pharmacology of meptazinol after parenteral administration in the elderly. European Journal of Clinical Pharmacology 31: 733–736, 1987

    Article  PubMed  CAS  Google Scholar 

  • Murray TG, Chiang ST, Koepke HH, Walker BR. Renal disease, age, and oxazepam kinetics. Clinical Pharmacology and Therapeutics 30: 805–809, 1981

    Article  PubMed  CAS  Google Scholar 

  • Nash RM, Stein L, Penno MB, Passananti GT, Vessel ES. Sources of interindividual variations in acetaminophen and antipyrine metabolism. Clinical Pharmacology and Therapeutics 36: 417–430, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nation RL, Learoyd B, Barber J, Triggs EJ. The pharmacokinetics of chlormethiazole following intravenous injection in the aged. European Journal of Clinical Pharmacology 10: 407–415, 1976

    Article  PubMed  CAS  Google Scholar 

  • Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. British Journal of Clinical Pharmacology 4: 439–448, 1977a

    Article  PubMed  CAS  Google Scholar 

  • Nation RL, Vine J, Triggs EJ, Learoyd B. Plasma level of chlormethiazole and two metabolites after oral administration to young and aged human subjects. European Journal of Clinical Pharmacology 12: 137–145, 1977b

    Article  PubMed  CAS  Google Scholar 

  • Nebert DW, Gonzalez FJ. Cytochrome P-450 gene expression and regulations.TIPS 165: 160–164, 1985

    Article  Google Scholar 

  • Netter P, Faure G, Regent MC, Prockral JA, Levy G. Salicylate kinetics in old age. Clinical Pharmacology and Therapeutics 38: 6–14, 1985

    Article  PubMed  CAS  Google Scholar 

  • Nies A, Robinson DS, Friedman MJ, Green R, Cooper TB, et al. Relationship between age and tricyclic antidepressant plasma levels. American Journal of Psychiatry 134: 790–793, 1977

    PubMed  CAS  Google Scholar 

  • Norbury HM, Franklin RA, Graham DF. Pharmacokinetics of the new analgesic, meptazinol, after oral and intravenous administration to volunteers. European Journal of Clinical Pharmacology 25: 77–80, 1983

    Article  PubMed  CAS  Google Scholar 

  • Norbury HM, Franklin RA, Graham DF, Sinha B. Pharmacokinetics of meptazinol after single and multiple oral administration to elderly patients. European Journal of Clinical Pharmacology 27: 223–226, 1984a

    Article  PubMed  CAS  Google Scholar 

  • Norbury HM, Franklin RA, Marrott PK, Warrington SJ. Pharmacokinetics of oral indoramin in elderly and middle-aged female volunteers. European Journal of Clinical Pharmacology 27: 247–249, 1984b

    Article  PubMed  CAS  Google Scholar 

  • O’Malley K, Crooks J, Duke E, Stevenson IH. Effects of age and sex on drug metabolism. British Medical Journal 3: 607–609, 1971

    Article  PubMed  Google Scholar 

  • Ochs HR, Greenblatt DJ, Friedman H, Burnstein ES, Locniskar A, et al. Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine and propranolol. Clinical Pharmacology and Therapeutics 41: 562–570, 1987

    Article  PubMed  CAS  Google Scholar 

  • Ochs HR, Greenblatt DJ, Otten H. Disposition of oxazepam in relation to age, sex, and cigarette smoking. Klinische Wochenschrift 59: 899–903, 1981

    Article  PubMed  CAS  Google Scholar 

  • Ochs HR, Greenblatt DJ, Verburg-Ochs B, Harmatz JS, Grehl H. Disposition of clotiazepam: influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol. European Journal of Clinical Pharmacology 26: 55–59, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ochs HR, Greenblatt DJ, Woo E, Smith TW. Reduced quinidine clearance in elderly persons. American Journal of Cardiology 42: 481–485, 1978

    Article  PubMed  CAS  Google Scholar 

  • Ogura C, Kishimoto A, Mizukawa R, Hazama H, Honma H, et al. Age differences in effect on blood pressure, flicker fusion frequency, salivation and pharmacokinetics of single oral dose of dothiepin and amitriptyline. European Journal of Clinical Pharmacology 25: 811–814, 1983

    Article  PubMed  CAS  Google Scholar 

  • Owen JA, Sitar DS, Berger L, Brownell L, Duke PC, et al. Age-related morphine kinetics. Clinical Pharmacology and Therapeutics 34: 364–368, 1983

    Article  PubMed  CAS  Google Scholar 

  • Paulsen O, Nilsson LG. Distribution of acetylator phenotype in relation to age and sex in Swedish patients. European Journal of Clinical Pharmacology 28: 311–315, 1985

    Article  PubMed  CAS  Google Scholar 

  • Pearson MW, Roberts CJC. Drug induction of hepatic enzymes in the elderly. Age and Ageing 13: 313–316, 1984

    Article  PubMed  CAS  Google Scholar 

  • Perucca E, Grimaldi R, Gatti G, Pirracchio GM, Crema F, et al. Pharmacokinetics of valproic acid in the elderly. British Journal of Clinical Pharmacology 17: 665–669, 1984

    Article  PubMed  CAS  Google Scholar 

  • Philip PA, Gayed SL, Rogers HJ, Crome P. Influence of age, sex and bodyweight on the dapsone acetylator phenotype. British Journal of Clinical Pharmacology 23: 709–713, 1987

    Article  PubMed  CAS  Google Scholar 

  • Piafsky KM, Borga O, Odar-Cederlöf I, Johansson C, Sjöqvist F. Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma alpha-l-acid glycoprotein. New England Journal of Medicine 229: 1435–1439, 1978

    Article  Google Scholar 

  • Pirttiaho HI, Sotaniemi EA, Ahlqvist J, Pitkänen U, Pelkonen RO. Liver size and indices of drug metabolism in alcoholics. European Journal of Clinical Pharmacology 13: 61–67, 1978

    Article  PubMed  CAS  Google Scholar 

  • Playfer JR, Baty JD, Lamb J, Powell C, Price-Evans DA. Age related differences in the disposition of acetanilide. British Journal of Clinical Pharmacology 6: 529–533, 1978

    Article  PubMed  CAS  Google Scholar 

  • Pontirolli AE, DePasqua A, Bouisolli L, Pozze G. Ageing and acetylator phenotype as determined by administration of sulphadimidine. European Journal of Clinical Pharmacology 28: 485–486, 1985

    Article  Google Scholar 

  • Posner J, Danhjof M, Teunissen MWE, Breimer DD, Whiteman PD. The disposition of antipyrine and its metabolites in young and elderly healthy volunteers. British Journal of Clinical Pharmacology 24: 51–55, 1987

    Article  PubMed  CAS  Google Scholar 

  • Quarterman CP, Kendall MJ, Jack DB. The effect of age on the pharmacokinetics of metoprolol and its metabolites. British Journal of Clinical Pharmacology 11: 287–294, 1981

    Article  PubMed  CAS  Google Scholar 

  • Randolph WC, Seamann JJ, Dickson B, Peace KE, Frank WO, et al. The effect of age on theophylline clearance in normal subjects. British Journal of Clinical Pharmacology 22: 603–605, 1986

    Article  PubMed  CAS  Google Scholar 

  • Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton U. Psychotropic drug use and the risk of hip fracture. New England Journal of Medicine 316: 363–369, 1987

    Article  PubMed  CAS  Google Scholar 

  • Regårdh CG, Landahl S, Larsson M, Lundborg P, Steen B, et al. Pharmacokinetics of metoprolol and its metabolite α-OH-metoprolol in healthy, non-smoking, elderly individuals. European Journal of Clinical Pharmacology 24: 221–226, 1983

    Article  PubMed  Google Scholar 

  • Richardson CJ, Blocka KLN, Ross SG, Verbeeck RK. Effect of age and sex on piroxicam disposition. Clinical Pharmacology and Therapeutics 37: 13–18, 1985

    Article  PubMed  CAS  Google Scholar 

  • Rikans LW, Notley BA. Age-related changes in hepatic microsomal drug metabolism are substrate dependent. Journal of Pharmacology and Experimental Therapeutics 220: 574–578, 1982

    PubMed  CAS  Google Scholar 

  • Rilschel WA. Age-dependent distribution of amobarbital: analog computer evaluation. Journal of the American Geriatrics Society 26: 540–543, 1978

    Google Scholar 

  • Robert C, Saint-Aubin A, Houin G, Padroni R, Ternier A, et al. Metabolisme de l’isomazide chez le vieillard, conséquences pratiques. La Revue de Gériatric 5: 211–216, 1980

    Google Scholar 

  • Robert J, Hoerni B. Age dependence of the early-phase pharmacokinetics of doxorubicin. Cancer Research 43: 4467–4469, 1983

    PubMed  CAS  Google Scholar 

  • Roberts MS, Rumble RH, Wanwimolruk S, Thomas D, Brooks PM. Pharmacokinetics of aspirin and salicylate in elderly subjects and in patients with alcoholic liver disease. European Journal of Clinical Pharmacology 25: 253–261, 1983

    Article  PubMed  CAS  Google Scholar 

  • Roberts RK, Wilkinson GR, Branch RA, Schener S. Effect of age and parenchymal liver disease on disposition and elimination of chlordiazepoxide (Librium). Gastroenterology 75: 479–485, 1978

    PubMed  CAS  Google Scholar 

  • Robertson DRC, Wood ND, Everest H, Monks K, Waller DG, et al. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. British Journal of Clinical Pharmacology 28: 61–69, 1989

    Article  PubMed  CAS  Google Scholar 

  • Rocci Jr ML, Vlasses PH, Cressman MD, Sirg MA, Plachetka J. Pharmacodynamics and disposition of labetalol in elderly vs young hypertensives. Abstract. Clinical Pharmacology and Therapeutics 41: 171, 1987

    Google Scholar 

  • Rooney L, Dendall MJ, Main A, Hosie J, John VA. Pharmacokinetics of pirprofen in young volunteers and elderly patients. European Journal of Clinical Pharmacology 29: 73–77, 1985

    Article  PubMed  CAS  Google Scholar 

  • Routledge PA, Chapman PH, Davis DM, Rawlins MD. Pharmacokinetics and pharmacodynamics of warfarin at steady state. British Journal of Clinical Pharmacology 8: 243–247, 1979

    Article  PubMed  CAS  Google Scholar 

  • Routledge PA, Stargel WW, Wagner GS, Shand DG. Increased alpha-1-acid glycoprotein and lidocaine disposition in myocardial infarction. Annals of Internal Medicine 93: 701–704, 1980

    PubMed  CAS  Google Scholar 

  • Roux A, Henry JF, Fouache Y, Chan NP, Hervy MP, et al. A pharmacokineuc study of acebutolol in aged subjects as compared to young subjects. Gerontology 29: 202–208, 1983

    Article  PubMed  CAS  Google Scholar 

  • Rubin PC, Scott PJW, Reid JL. Prazosin disposition in young and elderly subjects. British Journal of Clinical Pharmacology 12: 401–404, 1981

    Article  PubMed  CAS  Google Scholar 

  • Sager G, Hansteen V, Aakesson I, Jacobson S. Effect of heparin on serum binding of propranolol in the acute phase of myocardial infarction. British Journal of Clinical Pharmacology 12: 613–620, 1981

    Article  PubMed  CAS  Google Scholar 

  • Salem SAM, Rajjayabun P, Shepherd AMM, Stevenson JH. Reduced induction of drug metabolism in the elderly. Age and Ageing 7: 68–73, 1978

    Article  PubMed  CAS  Google Scholar 

  • Sartor G, Melander A, Schemén B, Wåhlin-Boll E. Influence of food and age on the single-dose kinetics and effects of tolbutamine and chlorpropamide. European Journal of Clinical Pharmacology 17: 285–293, 1980

    Article  PubMed  CAS  Google Scholar 

  • Scatina JA, Hicks D, Kraml M, Weidler D, Garg D, et al. Etodolac kinetics in the elderly. Clinical Pharmacology and Therapeutics 39: 550–553, 1986

    Article  PubMed  CAS  Google Scholar 

  • Schlenker LD. Food choices of the elderly. In Roe (Ed.) Drugs and nutrition in the geriatric patient, pp. 27–46, Churchill Livingstone, New York, 1984

    Google Scholar 

  • Schmucker DL. Drug disposition in the elderly: a review of the critical factors. Journal of the American Geriatrics Society 32: 144–149, 1984

    PubMed  CAS  Google Scholar 

  • Schmucker DL, Wang RD. Dietary restriction enhances monooxygenases in senescent male rats. Abstract. Gerontologist 28: 136A, 1988

    Google Scholar 

  • Schneck DW, Luderer JR, Pritchard JF, Vary JE, DeWitt FO, et al. A comparison of the intrinsic clearance of propranolol in young and elderly. Abstract. Clinical Pharmacology and Therapeutics 27: 284–285, 1980

    Google Scholar 

  • Schnegg M, Lauterburg BH. Quantitative liver function in the elderly assessed by galactose elimination capacity, aminopyrine demethylation and caffeine clearance. Journal of Hepatology 3: 164–171, 1986

    Article  PubMed  CAS  Google Scholar 

  • Schulz P, Turner-Tamiyasu K, Smith G, Giacomini KM, Blaschke TF. Amitriptyline disposition in young and elderly normal men. Clinical Pharmacology and Therapeutics 33: 360–366, 1983

    Article  PubMed  CAS  Google Scholar 

  • Schwartz JB, Abernethy DR. Responses to intravenous and oral diltiazem in elderly and younger patients with systemic hypertension. American Journal of Cardiology 59: 1111–1117, 1987

    Article  PubMed  CAS  Google Scholar 

  • Scott J, Poffenbarger PL. Pharmacogenetics of tolbutamide metabolism in humans. Diabetes 28: 41–51, 1979

    Article  PubMed  CAS  Google Scholar 

  • Shader RI, Greenblatt DJ, Ciraulo DA, Divoll M, Harmatz JS, et al. Effect of age and sex on disposition of desmethyldiazepam formed from its precursor clorazepate. Psychopharmacology 75: 193–197, 1981

    Article  PubMed  CAS  Google Scholar 

  • Shader RI, Greenblatt DJ, Harmatz JS, Frauke K, Koch-Weser J. Absorption and disposition of chlordiazepoxide in young and elderly male volunteers. Journal of Clinical Pharmacology 17: 709–718, 1977

    PubMed  CAS  Google Scholar 

  • Shami M, Elliott HL, Delman AW, Whiting B. The pharmacokinetics of mianserin. British Journal of Clinical Pharmacology 15: 313S–322S, 1983

    Article  PubMed  Google Scholar 

  • Shear NH, Spielberg SP, Grant DM, Tang BK, Kalow W. Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Annals of Internal Medicine 105: 179–184, 1986

    PubMed  CAS  Google Scholar 

  • Shepherd AMM, Hewick DS, Moreland TA, Stevenson IH. Age as a determinant of sensitivity to warfarin. British Journal of Clinical Pharmacology 4: 315–320, 1987

    Article  Google Scholar 

  • Shepherd AMM, Wilson N, Stevenson IH. Warfarin sensitivity in the elderly. In Crooks & Stevenson (Eds) Drugs and the elderly, pp. 199–209, University Park Press, Baltimore, 1979

    Google Scholar 

  • Sherlock S, Bearn AG, Billing AH, Paterson JCS. Splanchnic blood flow in man by the bromsulfalein method: the relation of peripheral plasma bromsulfalein level to the calculated flow. Journal of Laboratory and Clinical Medicine 35: 923–932, 1950

    PubMed  CAS  Google Scholar 

  • Shin SG, Juan D, Rammohan M. Theophylline pharmacokinetics in normal elderly subjects. Clinical Pharmacology and Therapeutics 44: 522–538, 1988

    Article  PubMed  CAS  Google Scholar 

  • Shull JH, Wilkinson GR, Johnson R, Schenker S. Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Annals of Internal Medicine 84: 420–425, 1976

    PubMed  CAS  Google Scholar 

  • Shultz P, Turner-Tamiyasu K, Smith G, Giacomini KM, Blaschke TF. Amitriptyline disposition in young and elderly normal men. Clinical Pharmacology and Therapeutics 33: 360–366, 1983

    Article  Google Scholar 

  • Singleton MA, Rosen JI, Fisher DM. Pharmacokinetics of fentanyl in the elderly. British Journal of Anaesthesia 60: 619–622, 1988

    Article  PubMed  CAS  Google Scholar 

  • Smith RE, Divoll M, Gillespie WR, Greenblatt DJ. Effect of subject age and gender on the pharmacokinetics of oral triazolam and temazepam. Journal of Clinical Psychopharmacology 3: 172–176, 1983

    PubMed  CAS  Google Scholar 

  • Smithard FJ, Langman MJS. The effect of vitamin supplementation upon antipyrine metabolism in the elderly. British Journal of Clinical Pharmacology 5: 181–185, 1978

    Article  PubMed  CAS  Google Scholar 

  • Sotaniemi EA, Huhti E. Half-life on intravenous tolbutamine in serum in patients in medical wards. Annals of Clinical Research 6: 146–154, 1974

    PubMed  CAS  Google Scholar 

  • Spector R, Choudhury AK, Chiang CK, Goldberg MJ, Ghoneim MM. Diphenhydramine in orientals and Caucasians. Clinical Pharmacology and Therapeutics 28: 229–234, 1980

    Article  PubMed  CAS  Google Scholar 

  • Spoelstra P, Teunissen MWE, Jansseus AR, Weeda B, Van Duiju W, et al. Antipyrine clearance and metabolite formation: the influence of liver volume and smoking. European Journal of Clinical Investigation 16: 321–327, 1986

    Article  PubMed  CAS  Google Scholar 

  • Stanski DR, Greenblatt DJ, Lowenstein E. Kinetics of intravenous and intramuscular morphine. Clinical Pharmacology and Therapeutics 24: 52–59, 1978

    PubMed  CAS  Google Scholar 

  • Stevenson IH, Salem SAM, Shepherd AMM. Studies on drug absorption and metabolism in the elderly. In Crooks & Stevenson (Eds) Drugs in the elderly, pp. 51–63. University Park Press, Baltimore, 1979

    Google Scholar 

  • Storstein L, Larsen A, Midtbø K, Soevareid L. Pharmacokinetics of calcium blockers in patients with renal insufficiency and in geriatric patients. Acta Medica Scandinavica 681 (Suppl.): 25–30, 1984

    PubMed  CAS  Google Scholar 

  • Summerbell J, Yelland C, Woodhouse K. The kinetics of plasma aspirin enlerase in relation to old age and frailty. Age and Ageing 19: 129–130, 1990

    Article  Google Scholar 

  • Sutter MA, Wood WG, Williamson LS, Strong R, Pickham K, et al. Comparison of the hepatic mixed function oxidase system of young, adult, and old non-human primates (Macaca mnemestrina). Biochemical Pharmacology 34: 2983–2987, 1985

    Article  PubMed  CAS  Google Scholar 

  • Swift CG, Homeida M, Halliwell M, Roberts CJC. Antipyrine disposition and liver size in the elderly. European Journal of Clinical Pharmacology 14: 149–152, 1978

    Article  PubMed  CAS  Google Scholar 

  • Swift CG, Swift MR, Ankier SI, Pidgen A, Robinson J. Single dose pharmacokinetics and pharmacodynamics of oral lorazepam in the elderly. British Journal of Clinical Pharmacology 20: 119–128, 1985

    Article  PubMed  CAS  Google Scholar 

  • Swift CG, Triggs EJ. Clinical pharmacokinetics in the elderly. In Swift (Ed.) Clinical pharmacology in the elderly, pp. 31–82, Marcel Dekker, New York, 1987

    Google Scholar 

  • Tinguely D, Baumann P, Conti M, Jonzier-Perez M, Schöpf J. Interindividual differences in the binding of antidepressives to plasma proteins: the role of the variants of alpha-l-acid glycoprotein. European Journal of Clinical Pharmacology 27: 661–666, 1985

    Article  PubMed  CAS  Google Scholar 

  • Traeger A, Kiesewetter R, Kunze M. Zur Pharmakokinetik von Phenobarbital bei Erwachsenen und Greisen. Deutsche Gesundheitswesen 29: 1040–1042, 1974

    Google Scholar 

  • Traeger A, Kunze M, Stein G, Ankermann H. Zur Pharmakokinetik von Indomethazin bei alten Menschen. Zeitschrift für Alternsforschung 27: 151–155, 1973

    PubMed  CAS  Google Scholar 

  • Triggs EJ, Nation RL, Long A, Ashley JJ. Pharmacokinetics in the elderly. European Journal of Clinical Pharmacology 8: 55–62, 1975

    Article  PubMed  CAS  Google Scholar 

  • Twum-Barima Y, Finnigan T, Habsh AI, Cape RDT, Carruthers SG. Impaired enzyme induction by rifampicin in the elderly. British Journal of Clinical Pharmacology 17: 595–597, 1984

    Article  PubMed  CAS  Google Scholar 

  • Upton RA, Williams RL, Kelly J, Jones RM. Naproxen pharmacokinetics in the elderly. British Journal of Clinical Pharmacology 18: 207–214, 1984

    Article  PubMed  CAS  Google Scholar 

  • Varga F, Fischer E. Age-dependent changes in blood supply of the liver and in the biliary excretion of eosin in rats. In Kitani (Ed.) Liver and ageing, pp. 327–340, Elsevier-North Holland, Amsterdam, 1978

    Google Scholar 

  • Verbeeck RK, Cardinal JA, Wallace SM. Effect of age and sex on the plasma binding of acidic and basic drugs. European Journal of Clinical Pharmacology 27: 91–97, 1984

    PubMed  CAS  Google Scholar 

  • Vestal RE, Cusack BJ. Pharmacology of ageing. In Schneider & Rowe (Eds) Handbook of the biology of ageing. 3rd ed., pp. 349–383, Academic Press, New York, 1990

    Chapter  Google Scholar 

  • Vestal RE, Cusack BJ, Mercer GD, Dawson GW, Park BK. Aging and drug interactions: I. Effect of cimetidine and smoking on the oxidation of theophylline and cortisol in healthy men. Journal of Pharmacology and Experimental Therapeutics 241: 488–500, 1987

    PubMed  CAS  Google Scholar 

  • Vestal RE, McGuire EA, Tobin JD, Andres R, Norris AH, et al. Aging and ethanol metabolism. Clinical Pharmacology and Therapeutics 21: 343–359, 1977

    PubMed  CAS  Google Scholar 

  • Veslal RE, Norris AH, Tobin JD, Cohen BH, Shock NW. et al. Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking. Clinical Pharmacology and Therapeutic: 18: 425–432, 1975

    Google Scholar 

  • Vestal RE, Wood AJJ. Influence of age and smoking on drug kinetics in man: studies using model compounds. Clinica Pharmacokinetics 5: 309–319, 1980

    Article  CAS  Google Scholar 

  • Vestal RE, Wood AJJ, Branch RA, Shand DG, Wilkinson GR Effects of age and cigarette smoking on propranolol disposition. Clinical Pharmacology and Therapeutics 26: 8–15, 1979a

    PubMed  CAS  Google Scholar 

  • Vestal RE, Wood AJJ, Shand DG, Reduced β-adrenoceptor sensitivity in the elderly. Clinical Pharmacology and Therapeutics 26: 181–186, 1979b

    PubMed  CAS  Google Scholar 

  • Wallace SM, Verbeeck RK. Plasma protein binding of drugs in the elderly. Clinical Pharmacokinetics 12: 41–72, 1987

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson GR, Shand DG. A physiological approach to hepatic drug metabolism. Clinical Pharmacology and Therapeutics 18: 377–390, 1975

    PubMed  CAS  Google Scholar 

  • Williams FM, Wynne H, Woodhouse KW, Rawlins MD. Plasma aspirin esterase: the influence of old age and frailty. Age and Ageing 18: 39–42, 1989

    Article  PubMed  CAS  Google Scholar 

  • Wilson LA, Lawson IR, Brans W. Multiple disorders in the elderly: a clinical and statistical study. Lancet 2: 841–843, 1962

    Article  PubMed  CAS  Google Scholar 

  • Wood AJJ, Vestal RE, Wilkinson GR, Branch RA, Shand DG. Effects of aging and cigarette smoking on antipyrine and in docyanide green elimination. Clinical Pharmacology and Therapeutics 26: 16–20, 1979

    PubMed  CAS  Google Scholar 

  • Woodford-Williams E, Alvarez AS, Webster D, Landless B, Dixon MP. Serum protein patterns in ‘normal’ and pathological ageing. Gerontologia 10: 86–99, 1964/65

    Article  Google Scholar 

  • Woodhouse KW, Mutch E, Williams FM, Rawlins MD, James OFW. The effect of age on pathways of drug metabolism in human liver. Age and Ageing 13: 328–334, 1984

    Article  PubMed  CAS  Google Scholar 

  • Woodhouse KW, Wynne HA. Age-related changes in liver size and hepatic blood flow: the influence on drug metabolism in the elderly. Clinical Pharmacokinetics 15: 287–296, 1988

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Cope LH, James OFW, Rawlins MD, Woodhouse KW. The effect of age and frailty upon acetanilide clearance in man. Age and Ageing 18: 415–418, 1989a

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, et al. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 9: 297–301, 1989b

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Mutch E, James OFW, Rawlins MD, Woodhouse KW. The effect of age on mono-oxygenase enzyme kinetics in rat liver microsomes. Age and Ageing 16: 153–158, 1987

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Mutch E, James OFW, Wright P, Rawlins MD, et al. The effect of age upon the affinity of microsomal mono-oxygense enzymes for substrate in human liver. Age and Ageing 17: 401–405, 1988

    Article  PubMed  CAS  Google Scholar 

  • Wynne HA, Mutch E, Williams FM, James OFW, Rawlins MD, et al. The relation of age to the acute effects of ethanol on acetanilide disposition. Age and Ageing 18: 123–126, 1989c

    Article  PubMed  CAS  Google Scholar 

  • Zybler-Katz E, Granit L, Stessman J, Levy M. Effects of age on the pharmacokinetics of dipyrone. European Journal of Clinical Pharmacology 36: 513–516, 1989

    Article  Google Scholar 

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Durnas, C., Loi, CM. & Cusack, B.J. Hepatic Drug Metabolism and Aging. Clin Pharmacokinet 19, 359–389 (1990). https://doi.org/10.2165/00003088-199019050-00002

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