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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.
목차
Abstract 실험방법 시료, 시약 및 기기 실험동물 약물투여 및 혈액 채취 니모디핀의 HPLC 분석 HPLC조건 및 혈장크로마토그램 CYP 효소 활성 억제실험 니모디핀의 약물동태학 분석 통계 처리 결과 및 고찰 티크로피딘의 CYP3A4 억제효과 티크로피딘이 니모디핀의 약물동태에 미치는 영향 결론 참고문헌