Pharmacokinetic drug interaction between fexofenadine and fluvastatin mediated by organic anion-transporting polypeptides in rats.
This study aimed to examine the transporter-mediated drug interaction between fexofenadine and fluvastatin in rats. Compared to the control group given fluvastatin alone, the concurrent use of fexofenadine (10 or 20mg/kg) prior to the oral administration of fluvastatin (5mg/kg) decreased the systemic exposure of fluvastatin by 17-51% in rats. Consequently, the bioavailability of oral fluvastatin was significantly lower (p<0.05) in the presence of fexofenadine compared to that from the control group. Furthermore, the intravenous pharmacokinetics of fluvastatin (2mg/kg) was significantly altered by the pretreatment with fexofenadine (20mg/kg, p.o.). The plasma clearance of fluvastatin was reduced by 44% in the presence of fexofenadine. The effect of fluvastatin on the pharmacokinetics of fexofenadine was also investigated in rats. The pretreatment with fluvastatin (5 or 10mg/kg) decreased AUC and C(max) of oral fexofenadine (10mg/kg) by 47-53% and 28-60%, respectively, while it did not affect the intravenous pharmacokinetics of fexofenadine. Given that both fluvastatin and fexofenadine can interact with organic anion-transporting polypeptides (OATPs) expressed in intestine and liver, the present results suggest the potential drug interaction between fluvastatin and fexofenadine via the competition for the OATP-mediated cellular transport pathway during intestinal absorption and/or hepatic uptake of drugs.
Qiang
Fu
F
BK21 Project Team, College of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-Gu, Gwangju 501-752, Republic of Korea.
Lee
Beom-Jin
BJ
Lee
Wonjae
W
Han
Hyo-Kyung
HK
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000493:pharmacokinetics*; D000077340:Fluvastatin; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D007211:Indoles / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D027361:Organic Anion Transporters / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D005229:Fatty Acids, Monounsaturated; D006634:Histamine H1 Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D027361:Organic Anion Transporters; D000077340:Fluvastatin; D016593:Terfenadine; C093230:fexofenadine