Abstract
Ropinirole is a selective non-ergoline dopamine D2 receptor agonist indicated for use in treating Parkinson’s disease. When taken as oral tablets, ropinirole is rapidly and almost completely absorbed, and it is extensively distributed from the vascular compartment. The bioavailability is approximately 50%. Ropinirole shows low plasma protein binding. The drug is inactivated by metabolism in the liver, and none of the major circulating metabolites have pharmacological activity. The principal metabolic enzyme is the cytochrome P450 (CYP) isoenzyme CYP1A2.
Ropinirole shows approximately linear pharmacokinetics when given as single or repeated doses, and is eliminated with a half-life of approximately 6 hours. Population pharmacokinetics have demonstrated that gender, mild or moderate renal impairment, Parkinson’s disease stage and concomitant illnesses or the use of several common concomitant medications have no effect on the pharmacokinetics of ropinirole. Clearance is slower for patients older than 65 years compared with those who are younger, and in women taking hormone replacement therapy compared with those who are not. The CYP1A2 inhibitor ciprofloxacin produced increases in the plasma concentrations of ropinirole when these 2 drugs were coadministered, but no interaction was seen with theophylline which, like ropinirole, is also a substrate for CYP1A2. There is no obvious plasma concentration-effect relationship for ropinirole.
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Korczyn AD, Brooks DJ, Brunt ER, et al. Ropinirole versus bromocriptine in the treatment of early Parkinson’s disease: a 6-month interim report of a 3-year study. 053 Study Group. Mov Disord 1998; 13: 46–51.
Korczyn AD, Brunt ER, Larsen JP, et al. A 3-year randomized trial of ropinirole and bromocriptine in early Parkinson’s disease [published erratum: Neurology 1999; 53: 1162]. Neurology 1999; 53: 364–70.
Rascol O, Brooks DJ, Brunt ER, et al. Ropinirole in the treatment of early Parkinson’s disease: a 6-month interim report of a 5-year levodopa-controlled study [056 Study Group]. Mov Disord 1998; 13: 39–45.
Rascol O, Brooks DJ, Korczyn AD, et al. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 2000; 342: 1484–91.
Rascol O, 056 Study Group. Motor complications in a 5-year comparative trial of the dopamine agonist ropinirole and L-dopa [abstract]. Mov Disord 2000; 15 Suppl. 3: 121: P634.
Dechant KL, Plosker GL. Ropinirole. CNS Drugs 1997; 8: 335–41.
Schrag AE, Brooks DJ, Brunt E, et al. The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson’s disease. Clin Neuropharmacol 1998; 21: 169–75.
Montastruc JL, Rascol O, Senard J-M. Treatment of Parkinson’s disease should begin with a dopamine agonist. Mov Disord 1999; 14: 725–30.
Phillips P. Several classes of new drugs emerging for Parkinson disease. JAMA 1999; 282: 929–31.
Lieberman A, Olanow CW, Sethi K, et al. A multicenter trial of ropinirole as adjunct treatment for Parkinson’s disease. Neurology 1998; 51: 1057–62.
Canesi M, Antonini A, Mariani CB, et al. An overnight switch to ropinirole therapy in patients with Parkinson’s disease. J Neural Transm 1999; 106: 925–9.
Iida M, Miyazaki I, Tanaka K-I, et al. Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res 1999; 838: 51–9.
Ogawa N, Miyazaki I, Tanaka K, et al. Dopamine D2 receptor mediated antioxidant and neuroprotective effects of ropinirole [abstract]. Parkinsonism Relat Disord 1999; 5 Suppl.: S81 (P-TU-123).
Galvez-Jimenez N, Khan T. Ropinirole and restless legs syndrome. Mov Disord 1999; 14: 890–2.
Ondo W. Ropinirole for restless leg syndrome. Mov Disord 1999; 14: 138–40.
Gottwald MD, Bainbridge JL, Dowling GA, et al. New pharmacotherapy for Parkinson’s disease. Ann Pharmacother 1997; 31: 1205–17.
Malmberg C. New therapies for Parkinson’s. Pharm Pract 1998; 14: 42–50.
Miyasaki JM. Ropinirole: a clinical profile. Todays Ther Trends 1998; 16: 177–92.
Ropinirole hydrochloride. In: Dollery C, editor. Therapeutic drugs. Vol. 2. 2nd ed. Edinburgh: Churchill Livingstone, 1999: R50–4.
Factor SA. Dopamine agonists. Med Clin North Am 1999; 83: 415–43.
Kuzel MD. Ropinirole: a dopamine agonist for the treatment of Parkinson’s disease. Am J Health Syst Pharm 1999; 56: 217–24.
Zesiewicz TA, Hauser RA. Ropinirole in the treatment of Parkinson’s disease. Expert Opin Invest Drugs 1999; 8: 697–710.
Eden RJ, Costall B, Domeney AM, et al. Preclinical pharmacology of ropinirole (SK&F101468-A), a novel dopamine D2 agonist. Pharmacol Biochem Behav 1991; 38: 147–54.
Coldwell MC, Boyfield I, Brown T, et al. Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2, D3 and D4 receptors expressed in Chinese Hamster Ovary Cells. Br J Pharmacol 1999; 127: 1696–702.
Levant B, Ling ZD, Carvey PM. Dopamine D3 receptors: relevance for drug treatment of Parkinson’s disease. CNS Drugs 1999; 12: 391–402.
Fears R, Bowen WP, Eden RJ, et al. Neurochemical selectivity and D3 affinity of the novel dopaminergic agonist ropinirole [abstract]. New Trends Clin Neuropharmacol 1994; 8: 298.
Jenner P. The rationale for the use of dopamine agonists in Parkinson’s disease. Neurology 1995; 45 Suppl. 3: S6–12.
Pearce RKB, Banerji T, Jenner P, et al. Effects of repeated treatment with L-dopa, bromocriptine and ropinirole in drug naïve MPTP-treated common marmosets [abstract]. Br J Pharmacol 1996; 118 Suppl.: 37P.
Brooks DJ, Torjanski N, Burn DJ. Ropinirole in the symptomatic treatment of Parkinson’s disease. J Neural Transm 1995; 45 Suppl.: 231–8.
Stocchi F, Destée A. Co-administration of ropinirole and domperidone during rapid dose escalation of the dopamine agonist. Parkinsonism Relat Disord 1998; 4: 183–8.
Acton G, Broom C. A dose rising study of the safety and effects on serum prolactin of SK & F 101468, a novel dopamine D2-receptor agonist. Br J Clin Pharmacol 1989; 28: 435–41.
de Mey C, Enterling D, Meineke I, et al. The effects of SK&F 101468, a novel D2-dopaminergic agonist on supine resting and stimulated circulatory and neuro-endocrine variables in healthy volunteers. Arzneimittelforschung 1990; 40: 7–12.
Swagzdis JE, Mico BA. Liquid chromatographic determination of 4(2-di-N,N-propylaminoethyl)-2-(3H)-indolone in rat, dog, and human plasma with ultraviolet detection. J Pharm Sci 1986; 75: 90–1.
de Mey C, Enterling D, Meineke I, et al. Interactions between domperidone and ropinirole, a novel dopamine D2-receptor agonist. Br J Clin Pharmacol 1991; 32: 483–8.
Ramji JV, Keogh JP, Blake TJ, et al. Disposition of ropinirole in animals and man. Xenobiotica 1999; 29: 311–25.
Boothman BR, Spokes EGS. Pharmacokinetic data for ropinirole [letter]. Lancet 1990; 336: 814.
Beerahee A, Nichols AI, Aluri J, et al. Population pharmacokinetics of ropinirole in patients with Parkinson’s disease. Br J Clin Pharmacol 1997; 43: 556P–7P.
Swagzdis JE, Wittendorf RW, DeMarinis RM, et al. Pharmacokinetics of dopamine-2 agonists in rats and dogs. J Pharm Sci 1986; 75: 925–8.
Jenner P, Tulloch I. The preclinical pharmacology of ropinirolereceptor interactions, antiparkinsonian activity and potential to induce dyskinesia. In: Olanow CW, Obeso JA, editors. Beyond the decade of the brain. Dopamine agonists in early Parkinson’s disease. Vol. 2. Royal Tunbridge Wells: Wells Medical, 1997: 115–28.
Wittendorf R, Mico B. Plasma protein binding and blood-to-plasma partition ratio of SKNF 101468 and SKNF 89124 in rat, dog and human blood. Report number BP004BA. Harlow (UK): SmithKline Beecham Pharmaceuticals, 1986. (Data on file).
Mimmo P, Joseph G, Carbonaro M, et al. In vitro plasma protein binding and blood cell partitioning of 3H-SKNF 101468 in monkey and human blood. Report number BP-1001. Harlow (UK): SmithKline Beecham Pharmaceuticals, 1992. (Data on file).
Ramji J, Keogh J, Taylor A, et al. Pharmacokinetics of ropinirole hydrochloride: absorption, distribution, metabolism and excretion of ropinirole hydrochloride after single and repeat administration to rats and monkeys. Jpn Pharmacol Ther 1996; 24 Suppl. 11: 47–60 (S-1765-S-1778).
Bloomer JC, Clarke SE, Chenery RJ. In vitro identification of the P450 enzymes responsible for the metabolism of ropinirole. Drug Metab Dispos 1997; 25: 840–4.
Beerahee A, Nichols A, Aluri J, et al. Population pharmacokinetics and pharmacokinetic/pharmacodynamic relationship of ropinirole in parkinsonian patients. Report number BF-1019. Harlow (UK): SmithKline Beecham Pharmaceuticals, 1995. (Data on file).
Zevin S, Benowitz NL. Drug interactions with tobacco smoking: an update. Clin Pharmacokinet 1999; 36: 425–38.
Hubble J, Koller WC, Atchison P, et al. Linear pharmacokinetic behaviour of ropinirole during multiple dosing in patients with Parkinson’s disease. J Clin Pharmacol 2000; 40: 641–6.
Urae A, Inokawa Y, Nishioka Y. Phase I clinical investigation of ropinirole hydrochloride (paper 3): pharmacokinetics after single and repeat oral administration to Japanese volunteers. Jpn Pharmacol Ther 1996; 24 Suppl. 11: 87–97 (S-1085-S-1815).
Miyashita N, Narabayashi H, Furukazu H, et al. Pharmacokinetic study of ropinirole hydrochloride (SK&F 101468) in patients with Parkinson’s disease. Jpn Pharmacol Ther 1996; 24 Suppl. 11: 291–303 (S-2009-S-2021).
Taylor AC, Beerahee A, Citerone DR, et al. Linear pharmacokinetics of ropinirole in patients with Parkinson’s disease. Br J Clin Pharmacol 1998; 45: 204P.
Brefel C, Thalamas C, Rayet S, et al. Effect of food on the pharmacokinetics of ropinirole in parkinsonian patients. Br J Clin Pharmacol 1998; 45: 412–5.
Massoud N. Pharmacokinetic considerations in geriatric patients. In: Benet LZ, Massoud N, Gambertoglio JG, editors. Pharmacokinetic basis for drug treatment. New York: Raven Press, 1984: 283–310.
Beerahee A, Nichols AI, Aluri J, et al. Population pharmacokinetics of ropinirole in parkinsonian patients. Int Pharm Abstr 1996; 33: 21.
Tornatore KM, Kanarkowski R, McCarthy TL, et al. Effect of chronic oral contraceptive steroids on theophylline disposition. Eur J Clin Pharmacol 1982; 23: 129–34.
Dalvi A, Ford B. Antiparkinsonian agents: clinically significant drug interactions and adverse effects, and their management. CNS Drugs 1998; 9: 291–310.
Wynalda MA, Wienkers LC. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos 1997; 25: 1211–4.
Bloomer JC, Clarke SE, Chenery RJ. An assessment of the potential of ropinirole, a dopamine receptor agonist, to inhibit various human cytochrome P450 enzymes [abstract]. Br J Pharmacol 1998; 124: 41P.
Bloomer JC, Taylor MA, Clarke SE, et al. An assessment of the potential of ropinirole and its N-despropyl and hydroxy metabolites to inhibit various human cytochrome P450 enzymes. Neurology 1999; 52 Suppl. 2: A410–11 (P05.039).
Taylor AC, Beerahee A, Citerone D, et al. Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with Parkinson’s disease. Pharmacotherapy 1999; 19: 150–6.
Taylor AC, Beerahee A, Citerone D, et al. The effect of steady-state ropinirole on plasma concentrations of digoxin in patients with Parkinson’s disease. Br J Clin Pharmacol 1999; 47: 219–22.
Dobbs RJ, O’Neill CJA, Deshmukh AA, et al. Serum concentration monitoring of cardiac glycosides. Clin Pharmacokinet 1991; 20: 175–93.
Wrighton SA, Vanden Branden M, Ring BJ. The human drug metabolising cytochromes P450. J Pharmacokinet Biopharm 1996; 24: 461–73.
Thalamas C, Taylor A, Brefel-Courbon C, et al. Lack of pharmacokinetic interaction between ropinirole and theophylline in patients with Parkinson’s disease. Eur J Clin Pharmacol 1999; 55: 299–303.
Cooper SM, Eagle S, Jones BA, et al. A study to investigate the effect of repeat oral doses of ciprofloxacin on steady-state ropinirole pharmacokinetics in parkinsonian patients. Report number 1018468/102. Harlow (UK): SmithKline Beecham Pharmaceuticals, 1998. (Data on file).
Adler CH, Sethi KD, Hauser RA, et al. Ropinirole for the treatment of early Parkinson’s disease. Neurology 1997; 49: 393–9.
Korczyn AD, Rascol O, Adler CH, et al. Dosing with ropinirole in a clinical setting [abstract]. Parkinsonism Relat Disord 1999; 5 Suppl.: S77 (P-TU-105).
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Kaye, C.M., Nicholls, B. Clinical Pharmacokinetics of Ropinirole. Clin Pharmacokinet 39, 243–254 (2000). https://doi.org/10.2165/00003088-200039040-00001
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DOI: https://doi.org/10.2165/00003088-200039040-00001