Bioequivalence of Two Commercial Preparations of trimethoprim/sulfamethoxazole: A randomized, single-dose, single-blind, crossover trial

Abstract

Background: Trimethoprinilsulfamethoxazole (TMP/SMX) is a combination of 2 antimicrobial agents that act synergistically, sequentially blocking 2 chemical reactions essential to bacterial survival. TMP/SMX is effective against organisms that are resistant to its separate components. Objective: The objective of this study was to comparethe bioavailability of 2 commercial preparations of T:MP/SMX 40/200 mg per 5-ml, oral suspension, used in Mexico for the treatment of bacterial infection. Methods: This study used a single-dose, randomized,single-blind, 2 × 2 crossover (2 dosing periods × 2 treatments) design to compare the 2 preparations. Healthy male volunteers aged 18 to 55 years received the trial and reference preparations in randomized sequence, under fasting conditions, with a 7-day washout period between dosing periods. Each preparation was administered as a single-dose 10-ml, oral suspension delivering 80 tng of TMP and 400 mg of SMX (equivalent to 2 doses of TMP/SMX 40/200 rig per 5 ml.). Pharmacokinetic (PK) parameters of C max AUC 0-t, and AUC 0-1 were determined for each component of each preparation. Schuirmann's unilateral double t test was performed. Null hypotheses indicating bioinequivalence ( P > 0.05) were rejected. Bioequivalence was determined if the quotient of the parameters of C max, AUC 0-t, and AUC 0-∞ were between 80% and 125%, at a power of 80% (α > 0.08). Results: Twenty-three of the 24 enrolled subjectscompleted the study. The subjects were all Hispanic, the mean (SD) age was 25 (6) years, and the mean (SD) body mass index was 22.54 (2.59) kg/m 2. Plasma concentration-time values of TMP and SMX were similar with both preparations. The null hypotheses of Schuirtnann's unilateral double t test were rejected, and results of the analyses of the PK parameters obtained 95% CIs within the predetermined range of bioequivalence (80%–125°10). The trial and reference preparations were statistically interchangeable and appeared to be bioequivalent. Conclusions: Based on similar PK profiles and statisticalanalyses, the trial and reference preparations were statistically interchangeable and appeared to be bioequivalent in this population of 23 healthy male volunteers in Mexico.