Lamorde Mohammed, Byakika-Kibwika Pauline, Tamale William S, Kiweewa Francis, Ryan Mairin, Amara Alieu, Tjia John, Back David, Khoo Saye, Boffito Marta, Kityo Cissy, Merry Concepta
Infectious Diseases Institute, Makerere University, College of Health Sciences, P.O. Box 22418, Kampala, Uganda.
AIDS Res Treat. 2012;2012:105980. doi: 10.1155/2012/105980. Epub 2012 Feb 20.
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.
我们研究了食物对一种含有富马酸替诺福韦二吡呋酯（TDF）/恩曲他滨/依非韦伦的专利固定剂量复方（FDC）片剂稳态药代动力学的影响。15名接受TDF/恩曲他滨/依非韦伦稳态给药的乌干达HIV-1患者在禁食状态下给药后入院进行24小时强化药代动力学采样。7天后，在给予TDF/恩曲他滨/依非韦伦并同时进食（19克脂肪）的情况下重复采血。采用液相色谱和串联质谱法测定血浆中的药物浓度。计算参数的几何平均比值（GMRs）和置信区间（CIs）（参考值，禁食）。对于依非韦伦，C(max)、AUC(0 - 24)和C(24)的GMRs（90% CIs）分别为1.47（1.24 - 1.75）、1.13（1.03 - 1.23）和1.01（0.91 - 1.11）。替诺福韦的相应GMRs为1.04（0.84 - 1.27）、1.19（1.10 - 1.29）和0.99（0.82 - 1.19），恩曲他滨的相应GMRs为0.83（0.76 - 0.92）、0.87（0.78 - 0.97）和0.91（0.73 - 1.14）。病情稳定的患者服用该FDC时无需限制饮食。出现中枢神经系统毒性的患者服用该FDC时应空腹。
