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 CY

• Status: Completed
• Trial end date: 2009-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Medicine Greifswald
• Treatments: Efavirenz; Ezetimibe; Reverse Transcriptase Inhibitors

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