Influence of OATP1B1 and CYP2C9 Genotypes on the Pharmacokinetics of Steady State Bosentan Before and During CYP3A4-inhibition by 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