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

University Medicine Greifswald

Status and phase

Completed

Phase 1

Conditions

Pharmacodynamics

Drug Interactions

Intestinal Transporter Expression

Pharmacokinetics

Treatments

Drug: Ezetrol (ezetimibe) multiple dose and Sustiva (efavirenz) single dose

Drug: Ezetrol (ezetimibe) multiple dose

Drug: Ezetrol (ezetimibe) and Sustiva (efavirenz) multiple dose

Drug: Sustiva (efavirenz) single dose

Study type

Interventional

Funder types

Other

Identifiers

NCT00810303

Efavirenz - 2008

Details and patient eligibility

About

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.

Enrollment

12 patients

Sex

All

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

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