Effect of resveratrol on the pharmacokinetics of oral and intravenous nicardipine in rats: possible role of P-glycoprotein inhibition by resveratrol.
The present study aimed to assess the effect of resveratrol on the bioavailability of nicardipine in rats. Nicardipine was administered orally (12 mg kg(-1)) or intravenously (4 mg kg(-1)) with or without oral administration of resveratrol (0.5, 2.5 or 10 mg kg(-1)). The oral administration of 2.5 or 10 mg kg(-1) of resveratrol significantly increased both the area under the plasma concentration-time curve (AUC) (P < 0.01, 111-126%) and the peak plasma concentration (Cmax) (P < 0.01, 105-121%), and significantly decreased the total body clearance (CL/F) (P < 0.01, 52.8-55.8%) of orally administered nicardipine. In contrast, resveratrol did not significantly change the pharmacokinetic parameters of i.v. nicardipine. Resveratrol significantly reduced rhodamine123 efflux via P-gp in MCF-7/ADR cells overexpressing P-gp. Resveratrol also inhibits CYP3A4, suggesting that the enhanced oral bioavailability of nicardipine by resveratrol may result from decreased P-gp-mediated efflux or inhibition of intestinal CYP3A4 metabolism. Based on these results, nicardipine dosage should be adjusted when given with supplements containing resveratrol.
Choi
Jun-Shik
JS
College of Pharmacy, Chosun University, Gwangju, Korea.
Choi
Byung-Chul
BC
Kang
Keon Wook
KW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005456:Fluorescent Dyes; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D020112:Rhodamine 123; D013267:Stilbenes / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D013267:Stilbenes; D020112:Rhodamine 123; D009529:Nicardipine; D000077185:Resveratrol