Related Experiment Video
Updated: May 10, 2026

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues
Published on: April 7, 2023
Clarithromycin substantially increases steady-state bosentan exposure in healthy volunteers
Christoph Markert1, Yvonne Schweizer, Regina Hellwig
1Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Aims:
The aim of this study was to assess the effect of the cytochrome P450 (CYP) 3A4 and organic anion-transporting polypeptide (OATP) 1B1 inhibitor clarithromycin on the pharmacokinetics of bosentan. We also aimed to evaluate the impact of CYP2C9 and SLCO1B1 (encoding for OATP1B1) genotypes and their combination.
Methods:
We assessed the effect of the OATP and CYP3A inhibitor clarithromycin on bosentan pharmacokinetics at steady state and concurrently quantified changes of CYP3A activity using midazolam as a probe drug. Sixteen healthy volunteers received therapeutic doses of bosentan (125 mg twice daily) for 14 days and clarithromycin (500 mg twice daily) concomitantly for the last 4 days, and bosentan pharmacokinetics was assessed on days 1, 10 and 14.
Results:
Clarithromycin significantly increased bosentan area under the plasma concentration-time curve of the dosing interval 3.7-fold and peak concentration 3.8-fold in all participants irrespective of the genotype. Clarithromycin also reduced CYP3A activity (midazolam clearance) in all participants; however, these changes were not correlated to the changes of bosentan clearance.
Conclusions:
Clarithromycin substantially increases the exposure to bosentan, suggesting that dose reductions may be necessary.
Related Concept Videos
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Pharmacokinetics: Drug–Drug Interactions
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
Hepatic Drug Clearance: Effect of Protein Binding
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow