Bioequivalence of two commercial preparations of trimethoprim/sulfamethoxazole: a randomized, single-dose, single-blind, crossover trial.
BACKGROUND
Trimethoprim/sulfamethoxazole (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 compare the 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 x 2 crossover (2 dosing periods x 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 bioin-equivalence (P > 0.05) were rejected. Bioequivalence was determined if the quotient of the parameters of C(max), AUC(0-t), and AUC(0-infinity) were between 80% and 125%, at a power of 80% (alpha > 0.08).


RESULTS
Twenty-three of the 24 enrolled subjects completed 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 Schuirmann'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 degrees 10). The trial and reference preparations were statistically interchangeable and appeared to be bioequivalent.


CONCLUSIONS
Based on similar PK profiles and statistical analyses, the trial and reference preparations were statistically interchangeable and appeared to be bioequivalent in this population of 23 healthy male volunteers in Mexico.
Alonso Campero
Rosalba
R
Asociación Mexicana para la lnvestigación Clinica, A. C., Pachuca, Mexico.
Bernardo Escudero
Roberto
R
Del Cisne Valle Alvarez
Doris
D
González de la Parra
Mario
M
Namur Montalvo
Salvador
S
Burke Fraga
Victoria
V
Silva Hernandez
Rodolfo
R
De Lago Acosta
Alberto
A
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D016001:Confidence Intervals; D018592:Cross-Over Studies; D005215:Fasting; D006801:Humans; D008297:Male; D008800:Mexico; D016037:Single-Blind Method; D013535:Suspensions; D013810:Therapeutic Equivalency; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D013535:Suspensions; D015662:Trimethoprim, Sulfamethoxazole Drug Combination