Journal article
Modest but Variable Effect of Rifampin on Steady-State Plasma Pharmacokinetics of Efavirenz in Healthy African-American and Caucasian Volunteers
Antimicrobial agents and chemotherapy, Vol.55(7), pp.3527-3533
07/2011
Handle:
https://hdl.handle.net/2376/100652
PMCID: PMC3122441
PMID: 21518840
Abstract
Efavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to receive 600 mg efavirenz/day or 600 mg efavirenz with 600 mg rifampin/day for 8 days, with plasma samples collected for pharmacokinetic analysis over 24 h on day 8. Treatments were then crossed over after at least a 2-week washout period, and procedures were repeated. Efavirenz concentrations were determined by high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were estimated by noncompartmental analysis. Efavirenz pharmacokinetic differences between treatment periods were evaluated by paired
t
test. The coefficients of variation in efavirenz plasma AUC
0-24
(area under the concentration-time curve from 0 to 24 h) were 50% and 56% in the absence and presence of rifampin, respectively. Of the 11 evaluable subjects (6 white, 5 black; 6 women, 5 men), the geometric mean AUC
0-24
ratio on/off rifampin (90% confidence interval) was 0.82 (0.72, 0.92), with individual AUC
0-24
ratios varying from 0.55 to 1.18. Five subjects had a 24-hour efavirenz concentration (
C
24
) of <1,000 ng/ml on rifampin. They were more likely to have received a lower dose in milligrams/kilogram of body weight and to have lower efavirenz AUC
0-24
values in the basal state. Although rifampin resulted in a modest reduction in efavirenz plasma exposure in subjects as a whole, there was high variability in responses between subjects, suggesting that efavirenz dose adjustment with rifampin may need to be individualized. Body weight and genetic factors will be important covariates in dosing algorithms.
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Details
- Title
- Modest but Variable Effect of Rifampin on Steady-State Plasma Pharmacokinetics of Efavirenz in Healthy African-American and Caucasian Volunteers
- Creators
- Awewura Kwara - Warren Alpert Medical School of Brown University, Providence, Rhode IslandKaren T Tashima - Warren Alpert Medical School of Brown University, Providence, Rhode IslandJulie B Dumond - University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaPamela Poethke - The Miriam Hospital, Providence, Rhode IslandJaclyn Kurpewski - The Miriam Hospital, Providence, Rhode IslandAngela D. M Kashuba - University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaMichael H Court - Tufts University School of Medicine, Boston, MassachusettsDavid J Greenblatt - Tufts University School of Medicine, Boston, Massachusetts
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.55(7), pp.3527-3533
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Identifiers
- 99900546619401842
- Language
- English
- Resource Type
- Journal article