Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Bosentan Before and During Clarithromycin
The aim of the present study is to assess the impact of the OATP1B1 genotype (SLCO1B1*15 vs. wild type; ~2% SLCO1B1*15 haplotypes in Caucasian population) and the CYP2C9 genotype (*2 and *3 allele vs. wild type; ~5% poor metabolisers in Caucasian population) on the pharmacokinetics of bosentan and the impact of CYP3A4-inhibition by clarithromycin on steady state bosentan which is a CYP3A4 inducer itself.
This study will focus on differential effects of genotypes and co-medication on the pharmacokinetics of bosentan at the metabolic and transport level. Participants will be genotyped for CYP2C9 (inclusion criterion), OATP1B1 (inclusion criterion), and CYP3A5 (no inclusion criterion).
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Steady State Bosentan Before and During CYP3A4-inhibition by Clarithromycin|
- AUC [ Time Frame: 0-infinity; dosing interval ] [ Designated as safety issue: No ]AUC of bosentan after first-dose, at steady-state and during clarithromycin therapy
- Cmax [ Time Frame: after first dose, at steady-state, during clarithromycin ] [ Designated as safety issue: No ]Cmax after the first dose of bosentan, at steady-state, during clarithromycin
|Study Start Date:||June 2011|
|Study Completion Date:||December 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Haplotypes of CYP2C9 and OATP1B1 characterisation of CYP2C9 (CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910)) and OATP1B1 (SLCO1B1*15 (rs2306283, rs4149056))
Other Name: Tracleer
Please refer to this study by its ClinicalTrials.gov identifier: NCT01425229
|University Hospital Heidelberg|
|Principal Investigator:||Gerd Mikus, Prof. Dr.||deputy head of department|