Akademik Veri Yönetim Sistemi
European Journal of Drug Metabolism and Pharmacokinetics, cilt.29, sa.2, ss.119-123, 2004 (SCI-Expanded)
This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. injection of CsA. Pharmacokinetic parameters were analyzed by nonparametric analysis of variance. Pretreatment with 60 or 90mg/kg diltiazem decreased the area under the blood CsA concentration-time curve (AUC) of oral CsA compared to control group (54.5% and 65.5% for AUC0-24, 57.6% and 62.2% for AUC0-∞, respectively, p<0.05). Mean CsA maximum concentration (Cmax) decreased from 0.4 ± 0.1 μg/ml to 0.1 ±0.0 μg/mL in rats pretreated with 90mg/kg diltiazem (p<0.05). The absolute bioavailability after oral administration (Fp.o) in the 60 or 90mg/kg diltiazem groups were lower than the control group (9.6% and 8.5% versus 22.6%). Pretreatment with 90mg/kg but not 60mg/kg of diltiazem increased the AUC0-∞, elimination half-life (t1/2) of intravenous CsA (116.0%, 219.2%, respectively, p<0.05) and decreased the intravenous CsA clearence (CLi.v) (62.9%, p<0.05). Diltiazem decreased the bioavailability of oral CsA, while it increased the bioavailability of intravenous CsA. One must consider this interaction when administering oral or intravenous CsA concomitantly with diltiazem.