Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration-time curve
研究概览
简要总结
The purpose of this study is to evaluate the influence of genetic polymorphism of cytochrome P450 3A5 on pharmacokinetics of maraviroc and its oxidative metabolites
详细描述
This study aims to evaluate the effects of CYP3A5 genotype on pharmacokinetics of maraviroc and its oxidative metabolites. A single oral dose of 300 mg maraviroc will be given to 24 eligible healthy individuals who will be screened and determined to have specific CYP3A5 genotype - 8 homozygous wild type (2 CYP3A5*1 alleles), 8 heterozygous (1 CYP3A5*1 allele and 1 mutant allele), and 8 without wild type genotype (2 mutant alleles). Blood samples will be drawn and urine samples will be collected immediately before and during a 32-hr period following the dose. The concentrations of maraviroc and its oxidative metabolites from the blood and urine samples will be measured and the pharmacokinetics of maraviroc and its metabolites will be compared among the three groups with different CYP3A5 polymorphic status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy with no acute medical illness
- •Willing to provide written informed consent
- •Age 18-65 years
- •Negative serum pregnancy test (females only) at screening and a negative urine pregnancy test (females only) on day of dosing
- •HIV seronegative at screening, as determined by any licensed ELISA
- •At screening, no evidence of hepatic or renal impairment (LFT's < 1.5 Upper Limit of Normal (ULN), creatinine clearance > than 60 ml/min, total bilirubin below ULN, AST and ALT below 1.5 ULN)
- •8 subjects with homozygous CYP3A5 allele *1 (wild type)
- •8 subjects with 1 CYP3A5*1 allele and 1 mutant allele
- •8 subjects with CYP3A5 allele other than *1
排除标准
- •Concomitant medication (prescription or over-the-counter) or herbal supplements for which there is a known risk of pharmacokinetic or pharmacodynamic drug interactions, including those that inhibit CYP3A4 as listed on the P450 Drug Interaction Table (http://medicine.iupui.edu/clinpharm/ddis/table.aspx)
- •History of postural hypotension or cardiovascular disease
- •Active medical or psychological condition that, in the opinion of the investigator, might put the volunteer at undue risk or interfere with the participation of the study
研究组 & 干预措施
Maraviroc
single oral administration of 300 mg maraviroc
干预措施: Maraviroc (Drug)
结局指标
主要结局
Area under the plasma concentration-time curve
时间窗: 0-32 hour post dose administration
次要结局
- Plasma peak concentration(0-32 hr post dose administration)
- Plasma half-life(0-32 hr post dose administration)
- Clearance(0-32 hr post dose administration)
- Urinary metabolic ratio(0-32 hr post dose administration)
研究者
Namandjé N. Bumpus, PhD
Assistant Professor
Johns Hopkins University