Trimethoprim/sulfamethoxazole does not affect the steady-state dispositionof indinavir

This study evaluates the safety and potential pharmacokinetic interaction b etween indinavir and trimethoprim/sulfamethoxazole (TMP/SMZ). In a randomiz ed, three-period crossover fashion, 12 healthy adults received 1 week of in dinavir sulfate 400 mg orally every 6 hours with placebo, TMP 160 mg/SMZ 80 0 mg orally every 12 hours with placebo and indinavir sulfate with TMP/SMZ. Plasma indinavir, SMZ, and TMP concentrations were determined after the la st dose of each treatment period. Concomitant administration resulted in a 17% decrease in geometric mean trough plasma indinavir concentrations (p = 0.032), an 18% increase in geometric mean AUC(0-12h) and C-max TMP values ( p = 0.031 and 0.030 respectively), and a 5% increase in geometric mean AUC( 0-12h) SMZ values (p = 0.039). None of these effects was considered clinica lly significant. The combination of indinavir sulfate and TMP/SMZ is genera lly well tolerated with no clinically significant pharmacokinetic interacti on being noted. Journal of Clinical Pharmacology, 1999;39:1077-1084 (C)1999 the American College of Clinical Pharmacology.