We investigated the effect of food on the steady-state pharmacokinetics of a proprietary fixed-dose combination (FDC) tablet\r\ncontaining tenofovir disoproxil fumarate (TDF)/emtricitabine/efavirenz. Fifteen Ugandan HIV-1 patients at steady-state dosing\r\nwith TDF/emtricitabine/efavirenz were admitted for 24-hour intensive pharmacokinetic sampling after dosing in the fasting\r\nstate. Blood sampling was repeated seven days later with TDF/emtricitabine/efavirenz administered with food (19 g fat). Drug\r\nconcentrations in plasma were determined by liquid chromatography and tandem mass spectrometry. Geometric mean ratios\r\n(GMRs) and confidence intervals (CIs) of parameters were calculated (reference, fasting). For efavirenz, GMRs (90% CIs) for\r\nCmax, AUC0-24, and C24 were 1.47 (1.24ââ?¬â??1.75), 1.13 (1.03ââ?¬â??1.23), and 1.01 (0.91ââ?¬â??1.11), respectively. Corresponding GMRs were\r\n1.04 (0.84ââ?¬â??1.27), 1.19 (1.10ââ?¬â??1.29), and 0.99 (0.82ââ?¬â??1.19) for tenofovir, 0.83 (0.76ââ?¬â??0.92), 0.87 (0.78ââ?¬â??0.97), and 0.91 (0.73ââ?¬â??1.14) for\r\nemtricitabine. Stable patients may take the FDC without meal restrictions. The FDC should be taken without food by patients\r\nexperiencing central nervous system toxicities.
Loading....