Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Antimicrob Agents Chemother. 2011 Jul;55(7):3527-33. doi: 10.1128/AAC.00980-10. Epub 2011 Apr 25.

Modest but variable effect of rifampin on steady-state plasma pharmacokinetics of efavirenz in healthy African-American and Caucasian volunteers.

Author information

  • 1Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. akwara@lifespan.org

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.

PMID:
21518840
[PubMed - indexed for MEDLINE]
PMCID:
PMC3122441
Free PMC Article

Images from this publication.See all images (4)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk