An update on the clinical pharmacokinetics of fexofenadine enantiomers. (3rd April 2018)

• Record Type: Journal Article
• Authors: Akamine, Yumiko; Miura, Masatomo
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 14:Number 4(2018)
• Page Start: 429
• Page End: 434
• Publication Date: 2018-04-03
• Subjects: Fexofenadine enantiomer -- organic anion transporting polypeptide -- P-glycoprotein -- pharmacokinetics -- stereoselectivity; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2018.1459565
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Introduction : Fexofenadine is administered as a racemic mixture of ( R )- and ( S )-enantiomers. The plasma concentrations of ( R )-fexofenadine in humans are about 1.5-fold higher than those of the ( S )-enantiomer. Such differences in the pharmacokinetics between fexofenadine enantiomers are likely to be dependent on stereoselectivity for affinity to drug-transporters. Areas covered : This review focuses on elucidation of differences in clinical pharmacokinetics between fexofenadine enantiomers. Expert opinion : Differences in pharmacokinetics between fexofenadine enantiomers were caused by organic anion transporting polypeptide (OATP) 2B1, with a minor contribution from P-glycoprotein (P-gp). In vitro studies using OATP2B1 cRNA showed that ( R )-fexofenadine uptake into oocytes is greater than ( S )-enantiomer uptake. P-gp inducers, carbamazepine, and inhibitors such as itraconazole and verapamil show greater effects on the pharmacokinetics of ( S )-fexofenadine. Apple juice and grape fruit juice, OATP2B1 inhibitors, significantly decrease the exposure of both fexofenadine enantiomers, particularly the ( S )-enantiomer, but do not change the t1/2 . Rifampicin significantly increases plasma concentrations of both enantiomers through inhibition of OATP1B3, whereas enantioselectivity of fexofenadine uptake by OATP1B3-expressing cells has not been observed. Combinations of multiple transporters such as OATP2B1 and P-gp facilitate enantioselective disposition of fexofenadine. Drug-transporters appear to be capable of chiral discrimination for transport of drugs with an asymmetric center.