Summary
The pharmacokinetics of the newer 1, 4 benzodiazepine temazepam were evaluated in 16 healthy subjects aged 18–92 years and in 15 cirrhotic patients, to ascertain the effect of ageing and liver disease. The data were analysed both by classic two compartment and by non-compartmental methods. The mean elimination half-life in the control subjects was 15.5 h, considerably longer than previous estimates. No correlation was found between age and pharmacokinetic parameters. The cirrhotic group showed no statistically significant difference in the pharmacokinetic parameters nor in the urinary recovery of the dose from the control group. Temazepam plasma protein binding was assessed in a second group of 9 cirrhotics of similar severity to the main group and in matched controls. When these binding data were applied to the mean clearance data, a modest although not statistically significant, reduction in free drug clearance was observed in the cirrhotic group. This study adds further support to the observation that drugs which undergo ether glucuronidation have normal elimination patterns in patients with liver disease. Temazepam may prove to be a useful hypnotic sedative in patients with liver disease.
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References
Roberts RK, Desmond PV, Schenker S (1979) Drug prescribing in hepatobiliary disease. Drugs 17: 198–212
Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR (1975) The effect of age and liver disease on the disposition of diazepam in adult man. J Clin Invest 55: 347–359
Roberts RK, Wilkinson GR, Branch RA, Schenker S (1978) The effect of age and liver disease on the disposition of chlordiazepoxide. Gastroenterology 75: 479–486
Shull HJ, Wilkinson GR, Johnson R, Schenker S (1976) Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 84: 420–425
Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, Wilkinson GR (1978) Effect of age and liver disease on disposition of lorazepam. Clin Pharmacol Ther 24: 411–419
Greenblatt DJ, Allen MD, Locniskan A, Harmatz J, Shader RI (1979) Lorazepam kinetics in the elderly. Clin Pharmacol Ther 26: 103–113
Greenblatt DJ, Divoll M, Harmatz JS, Shader RI (1981) Oxazepam kinetics — Effect of age and sex. J Pharmacol Exp Ther 30: 475–486
Schwarz HJ (1979) Pharmacokinetics of temazepam in man and several animal species. Br J Clin Pharmacol 8; 23S-29S
Greenblatt DJ, Divoll M, Abernethy DR, Ochs RH, Shader RI (1983) Clinical pharmacokinetics of the newer benzodiazepines. Clin Pharmacokinet 8: 233–252
Ghabrial H, Harman PJ, Mashford ML (1986) An HPLC assay for temazepam, oxazepam and their glucuronides in plasma, bile and urine. J Chromatogr (in press)
Yamaoka K, Nakagawa T, Uno T (1978) Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm 6: 547–558
Benet LZ, Galeazzi RL (1979) Non-compartmental determination of the steady state volume of distribution. J Pharm Sci 68: 1071–1974
Perrier D, Mayersohn M (1982) Noncompartmental determination of the steady state volume of distribution for any mode of administration. J Pharm Sci 71: 372–373
Conn HQ (1981) A peek at the Child-Turcotte classification. Hepatology 1: 673–676
Fuccella LM, Tosolini G, Moro E, Tamassia V (1972) Study of the physiological availability of temazepam in man. Int J Clin Pharmacol Ther Toxicol 6: 303–309
Fuccella LM, Bolcioni G, Tamassia V, Ferrario L, Tognoni G (1977) Human pharmacokinetics and bioavailability of temazepam administered in soft gelatin capsules. Eur J Clin Pharmacol 12: 383–386
Fuccella LM (1979) Bioavailability of temazepam in soft gelatin capsules. Br J Clin Pharmacol 8: 31S-35S
Bittencourt P, Richens A, Roseland PA, Wick JFC, Latham AN (1979) Pharmacokinetics of the hypnotic benzodiazepine temazepam. Br J Clin Pharmacol 8: 37S-38S
Divoll M, Greenblatt DJ, Harmatz JS, Shader RI (1981) Effect of age and gender on the disposition of temazepam. J Pharm Sci 70: 1104–1107
Jochemsen R, van Boxtel CJ, Hermans J, Breimer DD (1983) Kinetics of five benzodiazepine hypnotics in healthy subjects. Clin Pharmacol Ther 34: 42–47
Greenblatt DJ, Allen MD, Harmatz JS, Shader RI (1980) Diazepam disposition determinants. Clin Pharmacol Ther 27: 301–312
Allen MD, Greenblatt DJ, Harmatz JS, Shader RI (1980) Desmethyldiazepam kinetics in the elderly after oral prazepam. Clin Pharmacol Ther 28: 196–202
Azzollini F, Gazzaniga A, Lodola E, Natangelo R (1972) Elimination of chloramphenicol and thiamphenicol in subjects with cirrhosis of the liver. Int J Clin Pharmacol Ther Toxicol 6: 130–134
Kunin CM, Glazko AJ, Finland M (1959) Persistence of antibiotics in the blood of patients with acute renal failure II: Chloramphenicol and its metabolic product in the blood of patients with severe renal or hepatic cirrhosis. J Clin Invest 38: 1498–1508
Patwardhan RV, Johnson RF, Hoyumpa A, Sheehan JJ, Desmond PV, Wilkinson GR, Branch RA, Schenker S (1981) Normal metabolism of morphine in cirrhosis. Gastroenterology 81: 1006–1011
Gerkens JF, Desmond PV, Schenker S, Branch RA (1981) Hepatic and extrahepatic glucuronidation of lorazepam in the dog. Hepatology 1: 329–335
Jones DP (1981) Hypoxia and drug metabolism. Biochem Pharmacol 30: 1019–1023
Branch RA, Cotham R, Johnson R, Porter J, Desmond PV, Schenker S (1983) Periportal localization of lorazepam glucuronidation in the isolated perfused rat liver. J Lab Clin Med 102: 805–812
Desmond PV, James R, Schenker S, Gerkens JF, Branch RA (1981) Preservation of glucuronidation in carbon tetrachloride induced acute liver injury in rats. Biochem Pharmacol 30: 993–999
Gregus Z, Watkins JB, Thompson TN, Klaassen CD (1982) Resistance of some phase II biotransformation pathways to hepatotoxins. J Pharmacol Exp Ther 222: 471–479
James R, Desmond PV, Kupfer A, Schenker S, Branch RA (1981) The differential localization of various drug metabolising systems within the rat liver lobule as determined by the hepatotoxins allyl alcohol, carbon tetrachloride and bromobenzene. J Pharmacol Exp Ther 217: 127–132
Witaasek F, Bircher J, Huguenin P, Preisig R (1983) Abnormal glucuronidation of zomepirac in patients with cirrhosis of the liver. Hepatology 3: 415–422
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Ghabrial, H., Desmond, P.V., Watson, K.J.R. et al. The effects of age and chronic liver disease on the elimination of temazepam. Eur J Clin Pharmacol 30, 93–97 (1986). https://doi.org/10.1007/BF00614203
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DOI: https://doi.org/10.1007/BF00614203