title: Trimethoprim/sulfamethoxazole does not affect the steady-state disposition of indinavir.
abstract: This study evaluates the safety and potential pharmacokinetic interaction between indinavir and trimethoprim/sulfamethoxazole (TMP/SMZ). In a randomized, three-period crossover 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 AUC0-12 h and Cmax TMP values (p = 0.031 and 0.030, respectively), and a 5% increase in geometric mean AUC0-12 h 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.
authors.affiliation: College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08854-8020, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Sturgill
authors.forename: J R
authors.initials: JR
authors.lastname: Seibold
authors.forename: S E
authors.initials: SE
authors.lastname: Boruchoff
authors.forename: K C
authors.initials: KC
authors.lastname: Yeh
authors.forename: H
authors.initials: H
authors.lastname: Haddix
authors.forename: P
authors.initials: P
authors.lastname: Deutsch
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001663:Bilirubin / Q000097:blood; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D006261:Headache / Q000139:chemically induced; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D001663:Bilirubin