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).