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

The purpose of this study is to evaluate the effects of a chronic co-medication of efavirenz on pharmacokinetics and sterol-lowering effects of ezetimibe at steady-state in healthy subjects genotyped for ABCB1, ABCC2, CYP2B6 and UGT1A1.

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