Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects

Inclusion Criteria: * age: 18 - 45 years * sex: male and female * ethnic origin: Caucasian * body weight: 19 kg/m² to 27 kg/m² * good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state * written informed consent Exclusion Criteria: * known allergy to macrolide antibiotics * existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus * existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus * existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus * acute or chronic diseases which could affect drug absorption or metabolism * history of any serious psychological disorder * drug or alcohol dependence * positive drug or alcohol screening * smokers of 10 or more cigarettes per day * positive screening results for HIV, HBV and HCV * volunteers who are on a diet which could affect the pharmacokinetics of the drug * heavy tea or coffee drinkers (more than 1L per day) * lactation and pregnancy test positive or not performed * volunteers suspected or known not to follow instructions * volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study * volunteers liable to orthostatic dysregulation, fainting, or blackouts * blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study * participation in a clinical trial during the last 3 months prior to the start of the study * less than 14 days after last acute disease * any systemically available medication within 4 weeks prior to the intended first administration unless, because of the terminal elimination half-life, complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives) * repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin) * repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists) * intake of grapefruit containing food or beverages within 7 days prior to administration * known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation * subjects with severe allergies or multiple drug allergies