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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
University of Utah
Salt Lake City, Utah, United States
Daptomycin total, renal, and non-renal clearance
Total, renal, and non-renal clearance of daptomycin before and after administration of rifampin
Time frame: 14 days
Daptomycin Volume of Distribution
The volume of distribution of daptomycin before and after administration of rifampin
Time frame: 14 days
Daptomycin Elimination Rate Constant
The elimination rate constant of daptomycin before and after administration of rifampin
Time frame: 14 days
Daptomycin Free and Total Peak Concentrations
The free and total peak concentrations of daptomycin before and after administration of rifampin
Time frame: 14 days
Daptomycin Free and Total 24 hour Concentrations
The free and total 24 hour concentrations of daptomycin before and after administration of rifampin
Time frame: 14 days
Daptomycin Free and Total Area Under the Concentration-Time Curve (AUC) from 0 to 24 hours
The free and total AUC from 0 to 24 hours of daptomycin before and after administration of rifampin
Time frame: 14 days
Daptomycin Free and Total AUC from 0 to Infinity
The free and total AUC from 0 to infinity of daptomycin before and after administration of rifampin
Time frame: 14 days
Percent Protein Binding of Daptomycin
The percent protein binding of daptomycin before and after administration of rifampin
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Time frame: 14 days
P-glycoprotein Polymorphism
The effect of different P-glycoprotein polymorphisms on the pharmacokinetic profile of daptomycin before and after administration of rifampin will be assessed
Time frame: 14 days
Number of Participants with Adverse Events
Safety monitoring will be done by regular adverse event assessment, laboratory and vital sign monitoring, and physical exam.
Time frame: 45 days