A Randomized, Open-Label, Two-Sequence, Crossover Trial Evaluating the Bioequivalence, and Pharmacokinetics of Two Sulfamethoxazole/Trimethoprim Tablet Formulations in Healthy Chinese Volunteers Under Fasting Conditions.

Abstract

The compound sulfamethoxazole (SMZ)/trimethoprim (TMP), a dual-agent formulation comprising SMZ and TMP, exhibits synergistic bacteriostatic and bactericidal activity by disrupting folate metabolism pathways. This study assessed the bioequivalence (BE) of a generic compound SMZ/TMP tablet versus its innovator counterpart under fasting conditions (n = 24). In a meticulous, single-site, randomized, open-label, 2-period, 2-sequence crossover trial, 24 healthy Chinese adults were allocated to receive a single administration of either the test or reference medication, with a 7-day interval between doses. Venous blood samples were obtained pre-dose and at intervals up to 48 hours postdose for subsequent analysis. The plasma levels of SMZ and TMP were determined using a validated ultra-performance liquid chromatography-tandem mass spectrometry technique. Safety monitoring was conducted with precision throughout the trial for all subjects. The study's results indicated no significant differences in the peak plasma concentrations (C_max) of the drug when comparing the 2 SMZ/TMP formulations. Furthermore, the 90% confidence intervals for the ratios of the geometric means of C_max, the area under the curve from 0 time to the last quantifiable concentration point (AUC_0-t), and the area under the curve extrapolated to an infinite time point (AUC_0-∞) were all within the BE range accepted as 80%-125%. Notably, there were no reports of severe adverse events. These outcomes demonstrate the BE and favorable tolerability of the generic compound SMZ/TMP tablet in healthy Chinese subjects.