티크로피딘과 니모디핀과의 약동학적 상호작용
Pharmacokinetic Interaction between Ticlopidine and Nimodipine in Rats
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg)with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life (t1/2) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance (CLt). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.
Abstract
The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg)with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life (t1/2) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance (CLt). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.
참고문헌 (27)
- Scholz H, "Pharmacological aspects of calcium channel blockers", Cardiovasc. Drugs Ther, 10, pp.869~872 (1997)
- Epstein M, "Effects of calcium antagonists on renal hemodynamics", Am J Kidney Dis, 16, pp.10~14 (1990)
- Kazda S, "Cerebrovascular effects of the calcium antagonistic dihydropyridine derivative nimodipine in animal experiments", Arzneimittelforschung, 32, pp.331~338 (1982)
- nimodipine in rat, dog and monkey, "Arzneimittelforschung", 1985, 1781~1786
- nimodipine in rat, dog and monkey, "Arzneimittelforschung", 1985, 1787~1794
- Ramsch KD, "Overview on pharmacokinetics of nimodipine in healthy volunteer and in patients with subarachnoid hemorrhage", Neurochirurgia, 28, pp.74~78 (1985)
- Scherling D, "Biotransformation of nimodipine in rat, dog and monkey", Arzneimittelforschung, 41, pp.392~398 (1991)
- Guengerich FP, "Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrom P-450IIIA4", J Med Chem, 34, pp.1834~1844 (1991)
- Fuhr U, "Grapefruit juice increases oral nimodipine bioavailability", Int J Clin Pharmacol Ther, 36, pp.126~132 (1998)
- Zhang L, "P-glycoprotein restricted transport of nimodipine across blood-brain barrier", Acta Pharmacol Sin, 24, pp.903~906 (2003)
- Saltiel E, "Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutics efficacy in platelet-dependent disease states", Drugs, 34, pp.222~262 (1987)
- Gent M, "The Canadian American ticlopidine study(CATS) in thromboembolic stroke", Lancet, 1, pp.1215~1220 (1989)
- Hass Wk, "A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients", N Eng J Med, 321, pp.501~507 (1989)
- Janzon L, "Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study", J Intern Med, 227, pp.301~308 (1990)
- Haynes RB, "A critical appraisal of ticlopidine, a new antiplatelet agent. Effectiveness and clinical indications for prophylaxis of atherosclerotic events", Arch Intern Med, 152, pp.1376~1380 (1998)
- Ito MK, "Ticlopidine: a new platelet aggregation inhibitors", Clin Pharm, 11, pp.603~617 (1992)
- Verhaeghe R, "Prophylactic antiplatelet therapy in peripheral arterial disease", Drugs, 42, pp.51~57 (1991)
- Solomon DH, "Antithrombotic therapies for stroke prevention", Cur Opin Neurol, 7, pp.48~53 (1994)
- Buur T, "Pharmocokinetics and effect of ticlopidine on platelet aggregation in subjects with normal and impaired renal function", J Clin Pharmacol, 37, pp.108~115 (1997)
- Ko JW, "In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C9 and CYP2D6", Br J Clin Pharmacol, 49, pp.343~351 (2000)
- Gidal BE, "Evaluation of a potential enantioselective interaction between ticlopidine and warfarin in chronically anticoagulated patients", Ther Drug Monit, 17, pp.33~38 (1995)
- Shah J, "Effect of food and antacid on absorption of orally administered ticlopidine hydrochloride", J Clin Pharmacol, 30, pp.733~736 (1990)
- Qian M, "High-perfomance liquid chromatographic determinination of the calcium channel blocker nimodipine in monkey plasma", J Chromatogr, 578, pp.316~320 (1992)
- Mc Donnell CG, "Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro", Anaesthesia, 60, pp.747~753 (2005)
- Jun Shik Choi, "Enhanced Nimodipine Bioavailability After Oral Administration of Nimodipine with Morin, a Flavonoid, in Rabbits", Archives of Pharmacal Research, 29(4), pp.333~338 (2006), 대한약학회
- 박영길, "흰쥐에서 플루바스타틴이 딜티아젬 및 그 대사체인 데스아세틸딜티아젬의 약물태동에 미치는 영향", 약 학 회 지, 50(2), pp.118~123 (2006), 대한약학회
- 최준식, "플루바스타틴과 니카르디핀과의 약동학적 상호작용", 한국임상약학회지, 17(2), pp.65~69 (2007), 한국임상약학회