Effects of oral epigallocatechin gallate on the pharmacokinetics of nicardipine in rats.
Epigallocatechin gallate (EGCG), irreversibly inhibits cytochrome P450 (CYP) 3A subfamily and P-glycoprotein (P-gp) in vitro. This study investigated the effect of oral EGCG on the pharmacokinetics of intravenous and oral nicardipine in rats. Nicardipine was administered orally (12 mg/kg) or intravenously (4 mg/kg) with or without oral EGCG (0.5, 3 or 10 mg/kg) to rats. Compared to controls (without EGCG), the total areas under the plasma concentration-time curve (AUCs) of intravenous nicardipine were greater with oral EGCG. Compared to controls (without EGCG), the AUCs of oral nicardipine and the extent of absolute oral bioavailability (F) were also greater with oral EGCG. The above data suggest that oral EGCG inhibited both the hepatic CYP3A subfamily and intestinal P-gp.
Choi
Jun-Shik
JS
BK 21 Project Team and College of Pharmacy, Chosun University, Gwangju, 501-759, Korea.
Burm
Jin-Pil
JP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D016166:Free Radical Scavengers; D002392:Catechin; C045651:epigallocatechin gallate; D009529:Nicardipine