Inhibitory and inductive effects of rifampin on the pharmacokinetics of bosentan in healthy subjects

Clin Pharmacol Ther. 2007 Mar;81(3):414-9. doi: 10.1038/sj.clpt.6100075. Epub 2007 Jan 24.


This study was conducted to investigate the effect of rifampin on the pharmacokinetics of bosentan. Healthy male subjects received bosentan 125 mg b.i.d. for 6.5 days in the presence or absence of rifampin 600 mg once a day. In vitro experiments were performed to investigate the effect of rifampin on the uptake of bosentan into Chinese hamster ovary cells expressing the human organic anion-transporting polypeptide (OATP)1B1, -1B3, and -2B1. Following the first concomitant administration, there was a fivefold increase in bosentan trough concentrations. At steady state, concomitant rifampin significantly decreased exposure to bosentan by 58%. Rifampin potently inhibited the uptake of bosentan into cells expressing human OATP1B1 and -1B3. Rifampin decreased the exposure to bosentan consistent with its known cytochrome P450 enzyme-inductive properties. The initial increase in bosentan concentrations can be explained by an inhibitory effect of rifampin on hepatic drug transporters.

Publication types

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

MeSH terms

  • Adult
  • Algorithms
  • Antibiotics, Antitubercular / pharmacology*
  • Antihypertensive Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Bosentan
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Drug Interactions
  • Half-Life
  • Humans
  • Male
  • Mass Spectrometry
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Middle Aged
  • Rifampin / pharmacology*
  • Sulfonamides / pharmacokinetics*


  • Antibiotics, Antitubercular
  • Antihypertensive Agents
  • Sulfonamides
  • Cytochrome P-450 Enzyme System
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Bosentan
  • Rifampin