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KMID : 0941820070170010033
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Korean Journal of Clinical Pharmacy
2007 Volume.17 No. 1 p.33 ~ p.37
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Pharmacokinetic Interaction Between Diltiazem and Atorvastatin in Rats
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Jeong Joong-Wha
Kim Hyun-Yong
Choi Jun-Shik
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Abstract
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The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of diltiazem (15 mg/kg)
after oral administration of diltiazem with or without atorvastatin (0.5, 1.5 and 3.0 mg/kg) in rats. Coadministration of
atorvastatin increased significantly (p<0.05, 3.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration
(Cmax) of diltiazem compared to the control group. The total plasma clearance (CL/F) of diltiazem was
decreased significantly (p<0.05, 3.0 mg/kg) compared to the control group. The relative bioavailability (RB%) of diltiazem
was increased from 1.14- to 1.49-fold. Coadministration of atorvastatin did not significantly change the elimination
rate constant (Kel), terminal half-life (T1/2) and the time to reach the peak concentration (Tmax) of diltiazem. Based
on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be
due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal
mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa.
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KEYWORD
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Diltiazem, Atorvastatin, Pharmacokinetics, CYP3A4, P-gp
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