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  • Title: Reduced prehepatic extraction of nicardipine in the presence of pioglitazone in rats.
    Author: Choi JS, Koh YY, Chung JH, Choi DH, Han HK.
    Journal: J Pharm Pharmacol; 2008 Oct; 60(10):1403-7. PubMed ID: 18812034.
    Abstract:
    This study investigated the effect of pioglitazone on the pharmacokinetics of oral and i.v. nicardipine in rats. Pharmacokinetic parameters were determined after nicardipine was administered orally (12 mg kg(-1)) or i.v. (4 mg kg(-1)) with or without a single dose of oral pioglitazone (0.3 or 1.0 mg kg(-1)). Compared with the control group given nicardipine alone, coadministration of pioglitazone significantly decreased the total plasma clearance of orally administered nicardipine (by 40.4-46.3%, P < 0.05) and significantly increased the area under the plasma concentration-time curve (by 81.8-96.3%) and the peak plasma concentration, C(max) (by 56.5-66.8%). T(max) and the terminal plasma half-life of nicardipine were not affected, however. Coadministration of oral pioglitazone did not affect the pharmacokinetics of i.v. nicardipine, implying that pioglitazone may mainly decrease the prehepatic extraction of nicardipine during intestinal absorption. In conclusion, pioglitazone significantly enhanced the oral bioavailability of nicardipine in rats by reducing its presystemic clearance.
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