Comparative Bioavailability Of Two Tablet Formulations Of Emtricitabine/Tenofovir In Healthy, Fasting Volunteers: A Single-Dose, Randomized-Sequence, Open-Label Crossover Study

Objective: To evaluate the relative bioavailability of a new formulation of emtricitabine (EMT) 200 mg and tenofovir disoproxil fumarate (TNF) 300 mg and to compare with reference formulation to meet regulatory criteria in Argentina. Methods: A randomized-sequence, open-label, two-period crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of T or R formulations was followed by a 7-day washout period. Samples were collected at baseline, 0.25, 0.50, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 7, 12, 24, and 48 hours after administration. EMT and TNF were determined by LC-MS/ MS. Results: Geometric means (90% CI) C-max for EMT in test and reference were 1,891.22 (1,777.1 - 2,187.31) and 1,830.31 (1,721.19 - 2,134.01) ng/mL, the AUC(0-t) were 10,283.07 (9,624.29 - 11,566.34) and 10,518.76 (9,942.79 - 11,578.30) ng x h/mL and the AUC(0-infinity) were 10,615.14 (9,948.56 - 11,866.26) and 10,804.12 (10,221.04 - 11,864.85) ng x h/mL, respectively. For TNF test and reference, Cmax geometric means (CI range) were 202.91 (187.91 - 255.78) and 212.04 (195.98 - 264.87) ng/mL, AUC(0-t) were 1,429.96 (1,334.63 - 1,680.00) and 1,420.75 (1,326.76 - 1,622.18) ng x h/mL and AUC(0-infinity) were 1,657.11 (1,551.60 -1,921.75) and 1,631.84 (1,523.95 - 1,857.97), respectively. No differences were detected between the formulations. The test/reference ratios (90% CI) for C-max, AUC(0-t), and AUC(0-infinity) were 103.33% (95.7 - 111.6), 97.76% (93.6 - 102.1), and 98.25% (94.3 - 102.4) for EMT, and 95.70% (85.9 - 106.6), 95.20% (83.4 - 108.6) and 91.10% (80.7 - 102.7) for TNF. Conclusions: In this single-dose study, the EMT/TNF tablets (test formulation) met the standard 90% CI criterion for bioequivalence with the reference formulation.