Influence of Rifampin Co-Administration on the Pharmacokinetic Profile of Daptomycin

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.

Inclusion criteria

• Ability to provide informed consent
• If female of child bearing potential, on reliable method of contraception and negative pregnancy test at enrollment

Exclusion criteria

• 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