Pharmacokinetics and adverse effects of 20-mg/kg/day trimethoprim and 100-mg/kg/day sulfamethoxazole in healthy adult subjects

R. C. Stevens, Steven Laizure, C. L. Williams, D. S. Stein

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Abstract

The pharmacokinetics of trimethoprim-sulfamethoxazole were studied in 12 healthy adult subjects receiving trimethoprim at 20 mg/kg of body weight per day and sulfamethoxazole at 100 mg/kg/day, which is the conventional dose for treating Pneumocystis carinii pneumonia (PCP). Daily doses were evenly divided and orally administered every 6 h for 3 days. Trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole concentrations in serum and urine were measured by high-performance liquid chromatography. Five subjects withdrew from the study because of intolerable gastrointestinal and central nervous system toxicities. In the seven subjects that completed the study, the mean maximum serum drug concentrations after the last dose were 13.6 ± 2.0, 372 ± 64, and 50.1 ± 10.9 μg/ml for trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole, respectively. The mean half-lives were 13.6 ± 3.5, 14.0 ± 2.3, and 18.6 ± 4.3 h, respectively. Changes in absolute neutrophil count were significantly correlated with the minimum concentrations of trimethoprim and sulfamethoxazole in serum and trimethoprim area under the concentration-time curve (for all three parameters, r2 = 0.6 and P < 0.05). Our findings add to the evidence that serum drug concentrations in adults following the conventional dose of trimethoprim-sulfamethoxazole for PCP are excessive and contribute to certain adverse reactions. Further studies are indicated in patients to optimize the dosing regimen of trimethoprim-sulfamethoxazole in the treatment of PCP.

Original languageEnglish (US)
Pages (from-to)1884-1890
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume35
Issue number9
DOIs
StatePublished - Jan 1 1991

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Sulfamethoxazole
Trimethoprim
Sulfamethoxazole Drug Combination Trimethoprim
Healthy Volunteers
Pharmacokinetics
Pneumocystis Pneumonia
Serum
Pharmaceutical Preparations
Neutrophils
Central Nervous System
High Pressure Liquid Chromatography
Body Weight
Urine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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Pharmacokinetics and adverse effects of 20-mg/kg/day trimethoprim and 100-mg/kg/day sulfamethoxazole in healthy adult subjects. / Stevens, R. C.; Laizure, Steven; Williams, C. L.; Stein, D. S.

In: Antimicrobial Agents and Chemotherapy, Vol. 35, No. 9, 01.01.1991, p. 1884-1890.

Research output: Contribution to journalArticle

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