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

Conditions: Pharmacokinetics; Drug Interactions; Pharmacodynamics; Intestinal Transporter Expression

Summary: 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.


Eligibility criteria:
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