Effects of multiple-dose rifampicin 450 mg on the pharmacokinetics of fexofenadine enantiomers in Japanese volunteers

J Clin Pharm Ther. 2015 Feb;40(1):98-103. doi: 10.1111/jcpt.12213. Epub 2014 Sep 27.


What is known and objective: Rifampicin is a potent inducer of P-glycoprotein (P-gp) and inhibitor of organic anion-transporting polypeptides (OATPs), with fexofenadine acting as a substrate for both mechanisms. Simultaneous administration of single- or multiple-dose rifampicin 600 mg significantly increases the concentrations of fexofenadine enantiomers by inhibiting OATP transporters. However, the effects of rifampicin 450 mg are unknown. Here, we evaluated the effects of multiple doses of rifampicin 450 mg on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese volunteers.

Methods: In this randomized, two-phase, double-blind crossover study, 10 healthy volunteers received rifampicin 450 mg/day or placebo for 7 days. On day 7, fexofenadine 60 mg was co-administered simultaneously.

Results and discussion: Rifampicin significantly increased the mean area under the plasma concentration-time curve (AUC) of (R)- and (S)-fexofenadine (3.10-fold and 3.48-fold, respectively) and decreased the renal clearance of (R)- and (S)-fexofenadine (0.40-fold and 0.47-fold, respectively), causing marked differences in the mean amounts of these enantiomers excreted into the urine in the rifampicin phase (P < 0.001). These results indicated that multiple doses of rifampicin 450 mg may be sufficient to inhibit the renal influx transporter and OATP-mediated hepatic uptake of both enantiomers. Moreover, these effects may be greater than the P-gp-inductive effects of rifampicin. Therefore, the interactive mechanism of multidose rifampicin may occur through a combination of OATP and P-gp transporters, thereby altering the pharmacokinetics of fexofenadine enantiomers.

What is new and conclusions: In this study of rifampicin 450 mg, the interactive magnitude of the mean AUC values of fexofenadine enantiomers was higher than that observed in the previous study of rifampicin 600 mg, and no dose-dependent inhibitory effects of rifampicin were observed. These effects may be clinically significant in patients receiving fexofenadine and rifampicin.

Keywords: enantiomer; fexofenadine; organic anion-transporting polypeptides; pharmacokinetics; rifampicin; standard dose.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anti-Allergic Agents / pharmacokinetics*
  • Area Under Curve
  • Cross-Over Studies
  • Cytochrome P-450 CYP2B6 Inducers / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Interactions
  • Healthy Volunteers
  • Humans
  • Japan
  • Rifampin / administration & dosage*
  • Terfenadine / analogs & derivatives*
  • Terfenadine / pharmacokinetics


  • Anti-Allergic Agents
  • Cytochrome P-450 CYP2B6 Inducers
  • Terfenadine
  • fexofenadine
  • Rifampin