In vivo profiling and distribution of known and novel phase I and phase II metabolites of efavirenz in plasma, urine, and cerebrospinal fluid. Drug Metabolism and Disposition
Aouri et al. performed a quantitative metabolite profile analysis of efavirenz (EFV) comprising both phase I and phase II metabolites in plasma, cerebrospinal fluid (CSF), and urine samples in 71 human immunodeficiency virus patients taking EFV. They examined their relationships with the presence of certain genetic variants in different enzymes involved and with treatment discontinuation because of CNS toxicity. They identified the new metabolite 8OH-EFV-sulfate, which was present at high concentrations in all body compartments and demonstrated that the dominant circulating metabolites of EFV are not EFV primary oxidized products, but rather the downstream phase II EFV metabolites.
They conclude that the clinical importance of these previously unreported EFV metabolites in CSF and their potential contribution to the neuropsychological effects of EFV need to be examined in larger cohort studies.