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 Type
OBSERVATIONAL
Enrollment
16
* Administration of bosentan: 1 x 125 mg p.o. on day 1, 2 x 125 mg p.o. on day 2-14 * Administration of clarithromycin: 2 x 500 mg p.o. on day 11-14
University Hospital Heidelberg
Heidelberg, Germany
AUC
AUC of bosentan after first-dose, at steady-state and during clarithromycin therapy
Time frame: 0-infinity; dosing interval
Cmax
Cmax after the first dose of bosentan, at steady-state, during clarithromycin
Time frame: after first dose, at steady-state, during clarithromycin
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