Pharmacokinetic Drug Interaction Between Ezetimibe and Tacrolimus After Single Dose Administration in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for tacrolimus: AUC0-∞, Cmax
研究概览
简要总结
The purpose of this study is to confirm a significant influence of ezetimibe and tacrolimus on each others pharmacokinetics
详细描述
Hypercholesterolemia is a frequent finding in organ transplant recipients receiving immunosuppressive drugs such as tacrolimus. To prevent increased cardiovascular morbidity and mortality in these patients, co-medication with lipid-lowering statins is recommended. However, treatment with statins is limited in many patients by insufficient cholesterol-lowering efficacy, drug interactions and serious adverse drug reactions (e.g. rhabdomyolysis). These patients may benefit from comedication with the cholesterol absorption inhibitor ezetimibe. Since tacrolimus and ezetimibe were shown to be substrates of the efflux transporter ABCB1 (P-glycoprotein), drug interactions between both compounds may occur. Therefore, this clinical study in healthy subjects was initiated to evaluate the clinical relevance of drug/drug interactions between tacrolimus and ezetimibe according to the accepted bioequivalence approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age: 18 - 45 years
- •sex: male and female
- •ethnic origin: Caucasian
- •body weight: 19 kg/m² 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
排除标准
- •known allergy to macrolide antibiotics
- •existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- •existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- •existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of ezetimibe and sirolimus
- •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 screening results for HIV, HBV and HCV
- •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
研究组 & 干预措施
C
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe) and 1 capsule Prograf(R) (5 mg tacrolimus)
干预措施: 1 tablet Ezetrol(R) + 1 capsules Prograf(R) (Drug)
A
administration of 1 tablet Ezetrol(R) (10 mg ezetimibe)
干预措施: 1 tablet Ezetrol(R) (ezetimibe), MSD Sharp & Dohme GmbH, Germany (Drug)
B
administration of 1 capsule Prograf(R) (5 mg tacrolimus)
干预措施: 1 capsule Prograf(R) (tacrolimus), Astellas Pharma GmbH, Germany (Drug)
结局指标
主要结局
Primary characteristics: for ezetimibe: AUC0-∞, Cmax; for tacrolimus: AUC0-∞, Cmax
时间窗: September 2007 to November 2007
次要结局
- Second. characteristics: for ezetimibe: CLR, Ae (urine), Ae (feces); for ezetimibe glucuronide: AUC0-∞, Cmax, Ae (urine), Ae (feces); for ezetimibe, ezetimibe glucuronide and tacrolimus: AUC0-t, t½, tmax(September 2007 to November 2007)