Evaluation of Amlodipine Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Use pharmacokinetics to characterize the plasma concentration of amlodipine and its metabolite, 2-([4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl- 2-pyridyl]methoxy) acetic acid
研究概览
简要总结
The current study will evaluate the plasma pharmacokinetics of amlodipine in a cohort of 8 adult volunteers who are receiving regular hemodialysis treatment (HD) 3 days a week for 4 hours each day and have been taking a total daily dose of 5-10 mg of amlodipine besylate for >30 days as part of their usual care. Blood sampling will occur over 13 hours, with frequent sampling during HD and in the 4 hours after termination of HD treatment. The 8 subjects will all receive their prescribed total daily dose of 5-10 mg 5 hours prior to HD treatment. The pre-HD sample will also be sent for pharmacogenomics genotyping. Safety and pharmacodynamic assessments (blood pressure (BP) and heart rate (HR) assessments) will be performed throughout the study. Axiom Precision Medicine Research Array (Affymetrix, Santa Clara, CA) will be used to evaluate genotype of CYP3A4. CYP3A4 phenotype will be evaluated using the ratio of parent drug to metabolite. Non-compartmental analyses will be performed to compare maximum concentrations (Cmax), time to maximum concentration and area under the curve from time 0 to the last measurable sample (AUClast) between the two phases. Compartmental analyses will be performed to construct a model to explain time-dependent changes in amlodipine clearance. Monte Carlo simulations will be performed to compare amlodipine pharmacokinetic profiles on and off HD.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older
- •Indwelling tunneled catheter, AVF, AVG that is currently used for hemodialysis
- •Receiving in-center hemodialysis 3 days a week for 3-4.5 hours each treatment
- •Taking a total daily dose of 5-10 mg of amlodipine as prescribed by their physician
- •Hemoglobin ≥ 9.5 g/dL on most recent laboratory assessment prior to study
排除标准
- •Any condition that would not allow for arm BP to be taken
- •Hemoglobin < 9.5 g/dL on most recent lab prior to study
- •Patient is on a CYP3A4 inhibitor (most common in HD population include: amiodarone, clarithromycin, cyclosporine, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, nefazodone, tamoxifen, verapamil, and grapefruit juice).
结局指标
主要结局
Use pharmacokinetics to characterize the plasma concentration of amlodipine and its metabolite, 2-([4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl- 2-pyridyl]methoxy) acetic acid
时间窗: Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Use pharmacokinetics to characterize the change in plasma concentration of amlodipine and its metabolite, 2-(\[4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl- 2-pyridyl\]methoxy) acetic acid during and after HD
次要结局
- Characterize the Post-dialysis Rebound(post-dialysis (30 minutes, 2 hours and 4 hours))
- Characterize the Non-renal clearance phenotype and genotype(30 minutes)
研究者
Amy Barton Pai
Amy Pai, PharmD Associate Professor
University of Michigan