title: Effect of Food on the Steady-State Pharmacokinetics of Tenofovir and Emtricitabine plus Efavirenz in Ugandan Adults.
abstract: We investigated the effect of food on the steady-state pharmacokinetics of a proprietary fixed-dose combination (FDC) tablet containing tenofovir disoproxil fumarate (TDF)/emtricitabine/efavirenz. Fifteen Ugandan HIV-1 patients at steady-state dosing with TDF/emtricitabine/efavirenz were admitted for 24-hour intensive pharmacokinetic sampling after dosing in the fasting state. Blood sampling was repeated seven days later with TDF/emtricitabine/efavirenz administered with food (19 g fat). Drug concentrations in plasma were determined by liquid chromatography and tandem mass spectrometry. Geometric mean ratios (GMRs) and confidence intervals (CIs) of parameters were calculated (reference, fasting). For efavirenz, GMRs (90% CIs) for C(max), AUC(0-24), and C(24) were 1.47 (1.24-1.75), 1.13 (1.03-1.23), and 1.01 (0.91-1.11), respectively. Corresponding GMRs were 1.04 (0.84-1.27), 1.19 (1.10-1.29), and 0.99 (0.82-1.19) for tenofovir, 0.83 (0.76-0.92), 0.87 (0.78-0.97), and 0.91 (0.73-1.14) for emtricitabine. Stable patients may take the FDC without meal restrictions. The FDC should be taken without food by patients experiencing central nervous system toxicities.
authors.affiliation: Infectious Diseases Institute, Makerere University, College of Health Sciences, P.O. Box 22418, Kampala, Uganda.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Lamorde
authors.forename: Pauline
authors.initials: P
authors.lastname: Byakika-Kibwika
authors.forename: William S
authors.initials: WS
authors.lastname: Tamale
authors.forename: Francis
authors.initials: F
authors.lastname: Kiweewa
authors.forename: Mairin
authors.initials: M
authors.lastname: Ryan
authors.forename: Alieu
authors.initials: A
authors.lastname: Amara
authors.forename: John
authors.initials: J
authors.lastname: Tjia
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Concepta
authors.initials: C
authors.lastname: Merry