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

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 CYP2C19 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 * Contraindication against midazolam, ambrisentan, or SJW or any known intolerance to any of these substances or their additives