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http://dx.doi.org/10.4333/KPS.2004.34.1.015

Pharmacokinetic Interaction between Verapamil and Quercetin in Rabbits  

Choi, Jun-Shik (College of Pharmacy Chosun University)
Burm, Jin-Pil (Chosun Nursing College)
Publication Information
Journal of Pharmaceutical Investigation / v.34, no.1, 2004 , pp. 15-21 More about this Journal
Abstract
The pharmacokinetics of orally administered verapamil (10 mg/kg) was studied in six rabbits after 20 min pretreatment with quercetin ad coadministration of quercetin (2.0 mg/kg, 1 mg/g and 20 mg/kg, respectively). Pretreatment with quercetin significantly (p < 0.01, p < 0.05) increased the plasma concentration of verapamil. However, coadministration of quercetin showed no significantly effect on the pharmacokinetic parameters of verapamil. The elimination rate constant $(K_{el})$ of verapamil pretreated with quercetin (1 mg/kg and 20 mg/kg) was significantly (p < 0.05) reduced compared with control. The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of verapamil pretreated with quercetin (2.0 mg/kg, 10 mg/kg and 20 mg/kg) were increased significantly (p < 0.01, p < 0.05) compared with control. Pretreatment with quercetin (2.0 mg/kg, 10 mg/kg and 20 mg/kg) significantly (p < 0.01, p < 0.05) increased the relative bioavailability of verapamil to 159 - 219%. These results suggest that quercetin alters disposition of verapamil by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of verapamil should be adjusted when it is administered chronically with quercetin in a clinical situation.
Keywords
Verpamil; Quercetin; Pretreatment; Pharmacokinetics; Bioavaliability; P-glycoprotein; Fist-pass metabolism;
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