Mathias Anita A, Hinkle John, Menning Mark, Hui James, Kaul Sanjeev, Kearney Brian P
Gilead Sciences, Foster City, CA 94404, USA.
J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):167-73. doi: 10.1097/QAI.0b013e3181427835.
Efavirenz (EFV; 600 mg), emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) are preferred agents for treatment of HIV-1 infection in adults. This study evaluated the pharmacokinetics (PK) and bioequivalence of an investigational coformulation of EFV/FTC/TDF (test) single-tablet regimen compared with the commercially available individual dosage forms (EFV+FTC+TDF; reference treatment) in healthy subjects.
Subjects were randomized to 1 of 2 treatment sequences (test-->reference or reference-->test) in an open-label crossover study design. Study drug was administered under fasted conditions, and serial blood samples were obtained over 504 hours after oral administration of each treatment. Formulation bioequivalence was assessed in accordance with the US Food and Drug Administration bioequivalence criteria.
Forty-eight subjects were enrolled, and 45 completed the study, with all study treatments being generally well tolerated. For EFV (n = 44), the geometric mean ratios (90% confidence interval [CI]) for maximum concentration (C(max)), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC(0-last)), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC(inf)) were 99.9 (93.4 to 107), 95.7 (90.5 to 101), and 95.2 (88.9 to 102), respectively. For FTC (n = 45), the geometric mean ratios (90% CI) for C(max), AUC(0-last), and AUC(inf) were 88.8 (84.0 to 93.9), 98.0 (94.9 to 101), and 98.0 (94.9 to 101), respectively. For tenofovir (n = 45), the geometric mean ratios (90% CI) for C(max), AUC(0-last), and AUC(inf) were 91.5 (84.6 to 98.8), 99.3 (91.0 to 108), and 100 (93.2 to 108), respectively.
The coformulation of EFV/FTC/TDF is bioequivalent to administration of its individual components.
依非韦伦（EFV；600毫克）、恩曲他滨（FTC；200毫克）和替诺福韦酯富马酸盐（TDF；300毫克）是治疗成人HIV-1感染的首选药物。本研究评估了在健康受试者中，与市售单一剂型（EFV+FTC+TDF；参比治疗）相比，依非韦伦/恩曲他滨/替诺福韦酯（试验）单片复方制剂的药代动力学（PK）和生物等效性。
在开放标签交叉研究设计中，受试者被随机分配至2种治疗顺序之一（试验→参比或参比→试验）。研究药物在空腹条件下给药，在每次给药后504小时内采集系列血样。根据美国食品药品监督管理局生物等效性标准评估制剂生物等效性。
共纳入48名受试者，45名完成研究，所有研究治疗总体耐受性良好。对于依非韦伦（n = 44），最大浓度（C(max)）、从0至最后可定量浓度的血浆浓度-时间曲线下面积（AUC(0-last)）以及从0外推至无穷大的血浆浓度-时间曲线下面积（AUC(inf)）的几何平均比值（90%置信区间[CI]）分别为99.9（93.4至107）、95.7（90.5至101）和95.2（88.9至102）。对于恩曲他滨（n = 45），C(max)、AUC(0-last)和AUC(inf)的几何平均比值（90% CI）分别为88.8（84.0至93.9）、98.0（94.9至101）和98.0（94.9至101）。对于替诺福韦（n = 45），C(max)、AUC(0-last)和AUC(inf)的几何平均比值（90% CI）分别为91.5（84.6至98.8）、99.3（91.0至108）和100（93.2至108）。
依非韦伦/恩曲他滨/替诺福韦酯复方制剂与其各组分单独给药具有生物等效性。
