Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Daptomycin Free and Total Peak Concentrations
研究概览
简要总结
The purpose of this study is to understand how an antibiotic, rifampin, may change the blood levels of another antibiotic, daptomycin, in the body. In addition, the effect of polymorphisms in P-glycoprotein (a protein involved in the removal of daptomycin from the body) on the blood levels of daptomycin will be evaluated. The hypotheses are that rifampin will decrease the blood levels of daptomycin and that the effect will be greater for certain P-glycoprotein polymorphisms.
详细描述
This will be an open-label, sequential pharmacokinetic study in 12 healthy volunteers. After providing informed consent, participants meeting inclusion criteria will be administered daptomycin 6 mg/kg over 2 minutes and blood and urine samples will be collected over a 24 hour period after infusion. Following this, participants will be given a 13 day supply of rifampin 600 mg/day to be taken at home. After completion of the rifampin course, a second pharmacokinetic sampling will be performed (day 15 overall). Participants will be administered a dose of rifampin 600 mg then once again be administered daptomycin 6 mg/kg over 2 minutes and blood and urine samples will be collected over a second 24 hour period. A blood sample will be obtained at the first study visit for determination of each participant's P-glycoprotein genotype.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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
- •Ability to provide informed consent
- •If female of child bearing potential, on reliable method of contraception and negative pregnancy test at enrollment
排除标准
- •Obesity (body mass index > 30)
- •Creatinine clearance < 80 ml/min
- •Creatine phosphokinase > 2 times upper limit of normal at enrollment
- •Aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase > 3 times upper limit of normal at enrollment
- •History of liver disease or cirrhosis
- •History of congestive heart failure
- •Allergy or intolerance to rifampin or daptomycin
- •Need for concomitant non-study medications during the study period
- •Inability to abstain from grapefruit juice or herbal supplements (such as St. John's wort) during the study period
- •Receipt of study drugs within 30 days prior to enrollment
- •Pregnancy or lactation
- •Inability to adhere to study procedures
研究组 & 干预措施
Daptomycin and Rifampin
Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on the first study day Drug: Rifampin Rifampin 600 mg capsules will be given orally once daily for 14 days starting on study day 2 Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on study day 15
干预措施: Daptomycin (Drug)
Daptomycin and Rifampin
Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on the first study day Drug: Rifampin Rifampin 600 mg capsules will be given orally once daily for 14 days starting on study day 2 Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on study day 15
干预措施: Rifampin (Drug)
结局指标
主要结局
Daptomycin Free and Total Peak Concentrations
时间窗: 14 days
The free and total peak concentrations of daptomycin before and after administration of rifampin
Daptomycin Free and Total 24 hour Concentrations
时间窗: 14 days
The free and total 24 hour concentrations of daptomycin before and after administration of rifampin
Daptomycin Free and Total Area Under the Concentration-Time Curve (AUC) from 0 to 24 hours
时间窗: 14 days
The free and total AUC from 0 to 24 hours of daptomycin before and after administration of rifampin
Daptomycin Free and Total AUC from 0 to Infinity
时间窗: 14 days
The free and total AUC from 0 to infinity of daptomycin before and after administration of rifampin
Percent Protein Binding of Daptomycin
时间窗: 14 days
The percent protein binding of daptomycin before and after administration of rifampin
Daptomycin total, renal, and non-renal clearance
时间窗: 14 days
Total, renal, and non-renal clearance of daptomycin before and after administration of rifampin
Daptomycin Volume of Distribution
时间窗: 14 days
The volume of distribution of daptomycin before and after administration of rifampin
Daptomycin Elimination Rate Constant
时间窗: 14 days
The elimination rate constant of daptomycin before and after administration of rifampin
次要结局
- P-glycoprotein Polymorphism(14 days)
- Number of Participants with Adverse Events(45 days)
研究者
Russell Benefield
Pharmacist
University of Utah