Effects of oral epigallocatechin gallate on the oral pharmacokinetics of verapamil in rats.
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.
Chung
Joong-Hwa
JH
Chosun University, Gwangju, Republic of Korea.
Choi
Dong-Hyun
DH
Choi
Jun-Shik
JS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000031:analogs & derivatives / Q000493:pharmacokinetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D002392:Catechin; C016904:norverapamil; C045651:epigallocatechin gallate; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A