Effects of ticlopidine on pharmacokinetics of losartan and its main metabolite EXP-3174 in rats.

摘要: Losartan and antiplatelet agent ticlopidine can be prescribed concomitantly for prevention or therapy of cardiovascular diseases. Hence, the effects on pharmacokinetics losartan its active metabolite EXP-3174 were evaluated in rats. Ticlopidine (4 10 mg/kg po) was administered 30 min before administration (9 po 3 iv). The activity human CYP2C9 3A4 measured using CYP inhibition assay kit. P-gp rhodamine-123 retention MCF-7/ADR cells. (10 mg/kg) significantly increased areas under plasma concentration-time curves (AUCs) peak concentration (Cmax) oral mg/kg), as well AUCs EXP-3174. did not change intravenous (3 mg/kg). inhibited with IC50 values 26.0 32.3 μmol/L, respectively. relative cellular uptake unchanged. significant increase AUC by could attributed to CYP2C9- 3A4-mediated metabolism small intestine and/or liver. reduction renal elimination are unlikely causal factors.