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  • Title: Pharmacokinetic drug interaction between fexofenadine and fluvastatin mediated by organic anion-transporting polypeptides in rats.
    Author: Qiang F, Lee BJ, Lee W, Han HK.
    Journal: Eur J Pharm Sci; 2009 Jun 28; 37(3-4):413-7. PubMed ID: 19428223.
    Abstract:
    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.
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