Human Cytochrome P450 4F Enzymes and Drug Interactions
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Pharmacodynamics
研究概览
简要总结
Drug-drug interactions play an important role in clinical adverse events due to the prevalence of multi-drug therapy. Co-administration of warfarin and a statin has expanded substantially in the US over the last decades. The purpose of this study is to develop a mechanistic understanding of the role of a drug-metabolizing enzyme, CYP4F2, in the interaction between warfarin and statins. This study will test the hypothesis that lovastatin potentiates the anticoagulant effect of warfarin by inducing vitamin K-metabolizing enzyme CYP4F2 in humans, thus increasing warfarin's anticoagulant effect.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal baseline clinical laboratory results including coagulation panel (prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT)), liver function tests (ALT, AST, alkaline phosphatase and total bilirubin), kidney function tests (serum creatinine and BUN), lipid panel (cholesterol, LDL-C, HDL-C, and triglycerides), and blood creatine kinase
- •Minimum weight of 110 lbs and minimum hemoglobin level at 12.5 g/dL
- •Ability to understand the informed consent form
- •Willing to abstain from grapefruit products, alcohol, and physical contact sports
排除标准
- •History of intolerance, allergy, or hypersensitivity to study drugs warfarin and lovastatin or any substances contained in the medication
- •History of clotting disorders, stroke, hypertension, anemia, renal insufficiency, hepatic dysfunction, platelet dysfunction, gastrointestinal bleeding, or any recent bleeding episode or trauma within 6 months
- •History of significant medical conditions that the study physician believes would increase risk (e.g., additional bleeding disorders)
- •Genotype non-homozygous for CYP2C9*1 or genotype VKORC1-1639AA
- •History of significant alcohol abuse and/or illicit drug use
- •Tobacco use within the month preceding the study
- •Woman who is pregnant or breastfeeding
- •Women who are unable to maintain adequate birth control during the study
- •Post-menopausal women on estrogen replacement
- •Chronic statin or warfarin use
- •Taking concomitant medications, both prescription and non-prescription (including herbal products, over-the-counter medications, and multivitamins), known to alter lovastatin, warfarin, or vitamin K blood levels (women stabilized on hormonal methods of birth control will be allowed to participate, and subjects stabilized on antidepressant medications will be allowed to participate)
- •Recent use of antibacterial antibiotics
- •Recent blood donation or participation in other clinical studies within past 8 weeks
研究组 & 干预措施
Warfarin plus lovastatin
Warfarin plus lovastatin
干预措施: Warfarin (Drug)
Warfarin plus lovastatin
Warfarin plus lovastatin
干预措施: Lovastatin (Drug)
Warfarin plus placebo
Warfarin plus placebo
干预措施: Warfarin (Drug)
Warfarin plus placebo
Warfarin plus placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Pharmacodynamics
时间窗: Measurement will be performed before (baseline) and 2, 4, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, and 168h after co-administration of warfarin and lovastatin/placebo and during screening.
Measurement of Prothrombin time (PT) to assess the International Normalized Ratio (INR).
次要结局
- Pharmacokinetics(Sampling will be performed before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72, 96, 120, 144, and 168 h after co-administration of warfarin and lovastatin/placebo.)
研究者
Kim Brouwer, PharmD, PhD
Principal Investigator
University of North Carolina, Chapel Hill