Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin
- Conditions
- Drug InteractionsPharmacokinetics
- Interventions
- Registration Number
- NCT02097953
- Lead Sponsor
- University of Utah
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- Ability to provide informed consent
- If female of child bearing potential, on reliable method of contraception and negative pregnancy test at enrollment
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Daptomycin and Rifampin Daptomycin 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 Daptomycin and Rifampin 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
- Primary Outcome Measures
Name Time Method Daptomycin Free and Total Peak Concentrations 14 days The free and total peak concentrations of daptomycin before and after administration of rifampin
Daptomycin Free and Total 24 hour Concentrations 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 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 14 days The free and total AUC from 0 to infinity of daptomycin before and after administration of rifampin
Percent Protein Binding of Daptomycin 14 days The percent protein binding of daptomycin before and after administration of rifampin
Daptomycin total, renal, and non-renal clearance 14 days Total, renal, and non-renal clearance of daptomycin before and after administration of rifampin
Daptomycin Volume of Distribution 14 days The volume of distribution of daptomycin before and after administration of rifampin
Daptomycin Elimination Rate Constant 14 days The elimination rate constant of daptomycin before and after administration of rifampin
- Secondary Outcome Measures
Name Time Method P-glycoprotein Polymorphism 14 days The effect of different P-glycoprotein polymorphisms on the pharmacokinetic profile of daptomycin before and after administration of rifampin will be assessed
Number of Participants with Adverse Events 45 days Safety monitoring will be done by regular adverse event assessment, laboratory and vital sign monitoring, and physical exam.
Trial Locations
- Locations (1)
University of Utah
🇺🇸Salt Lake City, Utah, United States