Pharmacokinetic and Pharmacodynamic Interactions Between the Cholesterol-lowering Ezetimibe and the Non-nucleoside Reverse Transcriptase Inhibitor Efavirenz During Chronic Treatment in Healthy Volunteers With Reference to Intestinal Expression of CYP3A4, UGT1A1, ABCB1 and ABCC2

Inclusion Criteria:

• age: 18 - 45 years
• sex: male and female
• ethnic origin: Caucasian
• body weight: 19 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:

• existing cardiac or haematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
• existing hepatic and renal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
• existing gastrointestinal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics
• 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 anti-HIV-test, HBs-Ag-test or anti-HCV-test
• 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