Development and validation of an LC-MS/MS assay for the quantification of efavirenz in different biological matrices.

AIM: The non-nucleoside reverse transcriptase inhibitor efavirenz is one of the most prescribed antiretroviral therapeutics. Efavirenz-containing therapy has become associated with the occurrence of CNS side effects, including sleep disturbances, depression and even psychosis. RESULTS: The investigation of efavirenz distribution required the development of a versatile and sensitive method. In addition to plasma, quantification was required in brain tissue and phosphate-buffered saline. The assay presented here was linear from 1.9 to 500 ng/ml. Accuracy and precision ranged between 93.7 and 99.5%, and 1.5 and 5.6%, respectively. DISCUSSION: The method developed here represents a versatile, sensitive and easy-to-use assay. The assay has been applied to in vitro and in vivo samples demonstrating reliable efavirenz quantification in multiple matrices.

Simultaneous determination of efavirenz, rifampicin and its metabolite desacetyl rifampicin levels in human plasma.

A simple and rapid isocratic, high performance liquid chromatography (HPLC) assay employing solid phase extraction (SPE) for the simultaneous determination of the anti HIV drug, efavirenz, the anti-tuberculosis drug, rifampicin and the desacetyl metabolite of rifampicin in plasma from HIV/tuberculosis infected patients has been developed. Using a Zorbax SB-Phenyl reverse-phase analytical column with UV detection, good separation and detection of the drugs was attained within a 10min run time. Intra- and inter-assay precision RSD values were found to be less than 15% at the concentrations examined (0.1-20µg/mL). The LOQ was found to be 0.1µg/mL for each agent and the assay was found to generate a linear response up to 20µg/mL. This low cost assay can accurately detect efavirenz and rifampicin concentrations within a clinically relevant concentration range using standard chromatography equipment, making it particularly applicable to resource-limited settings.

Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.

BACKGROUND: The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients) study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Patients screened for R5 HIV-1 were randomized to receive efavirenz (600 mg once daily) or maraviroc (300 mg once or twice daily) with zidovudine-lamivudine. Coprimary end points were proportions of patients with a viral load <400 and <50 copies/mL at week 48; the noninferiority of maraviroc was assessed. RESULTS: The once-daily maraviroc arm was discontinued for not meeting prespecified noninferiority criteria. In the primary 48-week analysis (n = 721), maraviroc was noninferior for <400 copies/mL (70.6% for maraviroc vs 73.1% for efavirenz) but not for <50 copies/mL (65.3% vs 69.3%) at a threshold of -10%. More maraviroc patients discontinued for lack of efficacy (11.9% vs 4.2%), but fewer discontinued for adverse events (4.2% vs 13.6%). In a post hoc reanalysis excluding 107 patients (15%) with non-R5 screening virus by the current, more sensitive tropism assay, the lower bound of the 1-sided 97.5% confidence interval for the difference between treatment groups was above -10% for each end point. CONCLUSIONS: Twice-daily maraviroc was not noninferior to efavirenz at <50 copies/mL in the primary analysis. However, 15% of patients would have been ineligible for inclusion by a more sensitive screening assay. Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293) .