Influence of CYP3A4-induction by St. John's Wort on the Steady State Pharmacokinetics of Bosentan

• Status: Completed
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the present study is to assess the impact of the cytochrome P450 2C9 (CYP2C9) genotype (*2 and *3 allele versus wild type; ~3-5% poor metabolisers in Caucasian population) on the pharmacokinetics of bosentan and the impact of CYP3A4-induction by St. John's wort (SJW) on steady state bosentan which is a CYP3A4 inducer itself.

• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Gerd Mikus
• Treatments: Bosentan

Criteria

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 × upper limit of normal(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 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