Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats

Abstract

The effect of two kinds of 1,4-dihydropyridine calcium-channel blockers, nicardipine hydrochloride and nifedipine, on the disposition of carvedilol, was studied in rats. Blood samples were assayed for carvedilol levels using solid-phase extraction and high-performance liquid chromatography. The plasma carvedilol concentration was found to be significantly higher, and the area under the concentration-time curve up to 24 h (AUC0→24) was 6.7 and 3.0 times higher after simultaneous oral administration of 20 mg kg−1 carvedilol with 40 mg kg−1 nicardipine hydrochloride, or with 40 mg kg−1 nifedipine, respectively, than after administration of carvedilol alone. The pharmacokinetic interaction between carvedilol and dihydropyridine calcium-channel blockers is thought to be attributable to vasodilator-induced changes in hepatic first-pass metabolism, inhibition in the absorption barrier by P-glycoprotein and in the metabolism of carvedilol.