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KMID : 0941820090190010032
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Korean Journal of Clinical Pharmacy
2009 Volume.19 No. 1 p.32 ~ p.36
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Pharmacokinetic Interaction between Simvastatin and Nicardipine
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Choi Byung-Chul
Choi Jun-Shik
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Abstract
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The aim of this study was to investigate the effect of simvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with simvastatin (0.3 and 1.0 mg/kg). Compared with the control (given nicardipine alone), coadministration of simvastatin (1.0 mg/kg) significantly (p<0.05) increased the area under the plasma concentration (AUC) andpeak plasma concentration (Cmax) of nicardipine. The relative bioavailability (RB%) of nicardipine increased from 1.19-to 1.48-fold. However there were no significant changes in tmax, and t1/2 of nicardipine. The enhanced oral bioavailability of nicardipine might be due to an inbition of cytochrom P450 3A mediated-metabolism of nicardipine in the intestine and in the liver by simvastatin. Based on these results, the concurrent use of simvastatin significantly enhanced the oral exposure of nicardipine in rats. The dosage regimen of nicardipine should be taken into consideration for potential drug interaction when combined with simvastatin in clinics.
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KEYWORD
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Nicardipine, Simvastatin, Pharmacokinetics, CYP3A4, Rats
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