Decrease in the oral bioavailability of dabigatran etexilate after co-medication with rifampicin

Br J Clin Pharmacol. 2012 Sep;74(3):490-500. doi: 10.1111/j.1365-2125.2012.04218.x.


Aims: This study examined the effects of the CYP3A/P-glycoprotein inducer, rifampicin, on the pharmacokinetics of dabigatran following oral administration of the prodrug, dabigatran etexilate.

Methods: This was an open-label, fixed-sequence, four-period study in healthy volunteers. Subjects received a single dose of dabigatran etexilate 150 mg on day 1, rifampicin 600 mg once daily on days 2-8, and single doses of dabigatran etexilate on days 9, 16 and 23.

Results: Twenty-four subjects were treated, of whom 22 received all treatments. Relative to the reference (single dose of dabigatran etexilate alone; treatment A), administration of dabigatran etexilate following 7 days of rifampicin (treatment B) decreased the geometric mean (gMean) area under the concentration-time curve (AUC(0-∞)) and maximal plasma concentration (C(max)) of total dabigatran by 67 and 65.5%, respectively. The time to peak and the terminal half-life were not affected. The gMean ratio for the primary comparison (treatment B vs. treatment A) was 33.0% (90% confidence interval 26.5, 41.2%) for AUC(0-∞) and 34.5% (90% confidence interval 26.9, 44.1%) for C(max), indicating a significant effect on total dabigatran exposure (total pharmacologically active dabigatran represents the sum of nonconjugated dabigatran and dabigatran glucuronide). After a 7 day (treatment C) or 14 day washout (treatment D), the AUC(0-∞) and C(max) of dabigatran were reduced by 18 and 20%, and by 15 and 20%, respectively, compared with treatment A, which was considered not clinically relevant. The overall safety profile of all treatments was good.

Conclusions: Administration of rifampicin for 7 days resulted in a significant reduction in the bioavailability of dabigatran, which returned almost to baseline after 7 days washout.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Benzimidazoles / pharmacokinetics*
  • Biological Availability
  • Dabigatran
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Glucuronides / pharmacokinetics
  • Half-Life
  • Humans
  • Male
  • Prodrugs
  • Pyridines / pharmacokinetics*
  • Rifampin / pharmacology*
  • Young Adult


  • Benzimidazoles
  • Enzyme Inhibitors
  • Glucuronides
  • Prodrugs
  • Pyridines
  • Dabigatran
  • Rifampin