An update on the clinical pharmacokinetics of fexofenadine enantiomers

Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):429-434. doi: 10.1080/17425255.2018.1459565. Epub 2018 Apr 11.


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.

Keywords: Fexofenadine enantiomer; P-glycoprotein; organic anion transporting polypeptide; pharmacokinetics; stereoselectivity.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Anti-Allergic Agents / chemistry
  • Anti-Allergic Agents / pharmacokinetics
  • Biological Transport
  • Drug Interactions
  • Humans
  • Organic Anion Transporters / metabolism*
  • Stereoisomerism
  • Terfenadine / analogs & derivatives*
  • Terfenadine / chemistry
  • Terfenadine / pharmacokinetics


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-Allergic Agents
  • Organic Anion Transporters
  • SLCO2B1 protein, human
  • Terfenadine
  • fexofenadine