Maraviroc versus Efavirenz
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Study Design
The design was a phase two study comprised of four cohorts of HIV-positive patients. In this cohort patients were on the combined therapy of efavirenz/lamivudine/zidovudine while also receiving a single dose of maraviroc. (n=8) HIV-1 infected men aged 18-55 were enrolled to investigate the influence of efavirenz/lamivudine/zidovudine on the plasma pharmacokinetics of maraviroc. Subjects received a single oral dose of 300mg of maraviroc while concomitantly taking lamivudine 150mg/zidovudine 300mg BID, efavirenz 600mg was subsequently received the evening before maraviroc dosing QD. On the study day, all subjects received the maraviroc between 8-10h with water while concomitantly taking their self-provided ART regimen. Screening was done 21 days before dosing, and after the study day there was a follow-up period of 7-10 days after the study drug administration. Serial blood samples and urine samples were collected over 12h post dose. Geometric least squares ratios and 90% confidence intervals were estimated.
Study Results
Based on GMRs and 90% confidence intervals, when compared with maraviroc alone there was a 46.9% decrease in AUC12 (30.3, 72.4) and a 66.5% decrease in Cmax (40.8, 109) of maraviroc upon administration with the ART regimen of efavirenz/lamivudine/zidovudine + maraviroc.
This combination was generally well tolerated with only mild to moderate adverse events, and no adverse events leading to treatment discontinuation.
Study Conclusions
Per the authors, clinically significant alterations in maraviroc exposure can be attributed to the co-administration with other HIV ART.
References
Pozniak A, Boffito M, Russell D, Ridgway CE, Muirhead GJ. A novel probe drug interaction study to investigate the effect of selected antiretroviral combinations on the pharmacokinetics of a single oral dose of maraviroc in hiv-positive subjects. British Journal Of Clinical Pharmacology. 2008; S1: 54-59.
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