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An update on the clinical pharmacokinetics of fexofenadine enantiomers
- Source :
- Expert Opinion on Drug Metabolism & Toxicology. 14:429-434
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- 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.
- Subjects :
- Organic anion transporter 1
Organic Anion Transporters
Pharmacology
Toxicology
030226 pharmacology & pharmacy
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Anti-Allergic Agents
medicine
Humans
Drug Interactions
Terfenadine
ATP Binding Cassette Transporter, Subfamily B, Member 1
Fexofenadine
biology
Chemistry
Biological Transport
Stereoisomerism
General Medicine
Organic anion-transporting polypeptide
030220 oncology & carcinogenesis
biology.protein
Racemic mixture
Stereoselectivity
Enantiomer
medicine.drug
Subjects
Details
- ISSN :
- 17447607 and 17425255
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Expert Opinion on Drug Metabolism & Toxicology
- Accession number :
- edsair.doi.dedup.....4750918a4838c4d1daeec42874233c0a