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

healthy subjects

Inclusion Criteria:

• Good state of health (physically and mentally)
• Able to communicate well with the investigator, to understand and comply with the requirements of the study
• Voluntarily signed informed consent after full explanation of the study to the participant.
• No clinically relevant findings in any of the investigations of the pre-study examination, especially aminotransferase elevations ≥ 3 × ULN. Minor deviations of other laboratory values from normal range may be acceptable, if judged by the investigator to be of no clinical relevance.
• Known genotype for CYP2C9 and OATP1B1 polymorphism.
• Agreement to abstain from alcoholic beverages during the time of the study.
• Females must agree to use a reliable contraception (Pearl Index <1%), e.g. double barrier method.

Exclusion Criteria:

• Any regular drug treatment within the last two months, except for oral contraceptives in female volunteers and L-thyroxine.
• Any intake of a substance known to induce or inhibit drug metabolising enzymes or drug transporters within a period of less than 10 times the respective elimination half-life or 2 weeks, whatever is longer
• Any participation in a clinical trial within the last month before inclusion
• Any physical disorder which could interfere with the participant's safety during the clinical trial or with the study objectives
• Any acute or chronic illness, or clinically relevant findings in the pre-study examination, especially: a) any condition, which could modify absorption, distribution, metabolism, or excretion of the drug regimen under investigation b) Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions
• Regular smoking
• Blood donation within 6 weeks before first study day
• Excessive alcohol drinking (more than approximately 20 g alcohol per day)
• Inability to communicate well with the investigator due to language problems or poor mental development
• Inability or unwillingness to give written informed consent
• Known or planned pregnancy or breast feeding
• Pre-existing moderate or severe liver impairment