Trimethoprim/sulfamethoxazole does not affect the steady-state disposition of indinavir

This study evaluates the safety and potential pharmacokinetic interaction between indinavir and trimethoprim/sulfamethoxazole (TMP/SMZ). In a randomized, three-period crassover fashion, 12 healthy adults received 1 week of indinavir sulfate 400 mg orally every 6 hours with placebo, TMP 160 mg/SMZ 800 mg orally every 12 hours with placebo, and indinavir sulfate with TMP/SMZ. Plasma indinavir, SMZ, and TMP concentrations were determined after the last 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 clinically significant. The combination of indinavir sulfate and TMP/SMZ is generally well tolerated, with no clinically significant pharmacokinetic interaction being noted. (C) 1999 the American College of Clinical Pharmacology.