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  • Title: Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats.
    Author: Chung JH, Choi DH, Choi JS.
    Journal: Biopharm Drug Dispos; 2009 Mar; 30(2):90-3. PubMed ID: 19226653.
    Abstract:
    Verapamil is known to be a P-glycoprotein (P-gp) substrate and norverapamil is formed via hepatic cytochrome P450 (CYP 3A) in the rat. Epigallocatechin gallate (EGCG), a flavonoid, was reported to be an inhibitor of both P-gp and CYP3A. Hence, it could be expected that EGCG could alter the pharmacokinetics of verapamil. In this study, 9 mg/kg verapamil was administered orally to Sprague-Dawley rats 30 min after the oral administration of 2 and 10 mg/kg of oral EGCG. Compared with the controls, the AUC values of both verapamil (74.3% and 111% increase for 2 and 10 mg/kg EGCG, respectively) and norverapamil (51.5% and 87.2% increase for 2 and 10 mg/kg EGCG, respectively) were significantly greater in the presence of EGCG. However, compared with the controls, both the AUC and the relative bioavailability of verapamil were significantly (p<0.01) increased by 74.3-111% in the presence of EGCG. The likely explanation is inhibition of P-gp. Inhibition of CYP3A would increase the AUC of verapamil but decrease the AUC of norverampil. However, inhibition of P-gp would lead to an increase of AUC of both verapamil and norverapamil.
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