Semisimultaneous Midazolam Administration to Evaluate the Time Course of CYP3A Activation by a Single Oral Dose of Efavirenz.

This study aimed to assess whether a single oral dose of the nonnucleoside reverse transcriptase inhibitor efavirenz can alter CYP3A in vivo. In 12 healthy participants individual CYP3A activity was quantified using a semisimultaneous methodology (midazolam orally and 6 hours later intravenously) both alone and during a period of 22 days after a single oral dose of 400 mg efavirenz. Twelve hours after efavirenz administration, midazolam apparent oral clearance was significantly increased by 70%, and midazolam systemic clearance after intravenous administration was significantly increased by 27%.

No evidence for induction of ABC transporters in peripheral blood mononuclear cells in humans after 14 days of efavirenz treatment.

Intracellular concentrations of antiretroviral drugs in peripheral blood mononuclear cells (PBMCs) are an important determinant of therapeutic success. In vitro data indicate that efavirenz induces several ATP-binding cassette (ABC) transporters, and pharmacogenetic studies found an association between ABCB1(C3435T) and efavirenz exposure and between this polymorphism and improved virological outcomes. We therefore aimed to clarify whether efavirenz also induces ABC transporters in vivo in PBMCs and whether intracellular concentrations might be altered after induction.