Multiple-dose pharmacokinetics of 12 milligrams of trimethoprim and 60 milligrams of sulfamethoxazole per kilogram of body weight per day in healthy volunteers

R. C. Stevens, Steven Laizure, P. L. Sanders, D. S. Stein

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21 Citations (Scopus)

Abstract

The disposition of 12 mg of trimethoprim and 60 mg of sulfamethoxazole per kg of body weight in six healthy male volunteers is described. The daily dose was evenly divided and administered orally every 6 h for 13 consecutive doses. Individual drug components were assayed by high-performance liquid chromatography. Steady-state concentrations in serum for trimethoprim and sulfamethoxazole were within the purported therapeutic ranges for treating Pneumocystis carinii pneumonia. Co-trimoxazole was well tolerated, and no subject withdrew from the study because of toxicity. Comparison of the pharmacokinetic parameters in this study with those of our previous findings indicates that the elimination of trimethoprim-sulfamethoxazole follows a first-order process within the dose ranges assessed. Administration of 15- to 20-mg/kg trimethoprim and 75- to 100-mg/kg sulfamethoxazole in four evenly divided doses for the first 24 h followed by 12 and 60 mg/kg/day, respectively, for the remainder of therapy rapidly attains concentrations in serum within the proposed P. carinii pneumonia therapeutic range. Clinical trials are indicated to evaluate this dosing scheme, which may decrease exposure to potentially excessive concentrations of trimethoprim and sulfamethoxazole.

Original languageEnglish (US)
Pages (from-to)448-452
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume37
Issue number3
DOIs
StatePublished - Jan 1 1993

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Sulfamethoxazole
Trimethoprim
Sulfamethoxazole Drug Combination Trimethoprim
Healthy Volunteers
Pharmacokinetics
Body Weight
Pneumocystis Pneumonia
Serum
Therapeutics
High Pressure Liquid Chromatography
Clinical Trials
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Multiple-dose pharmacokinetics of 12 milligrams of trimethoprim and 60 milligrams of sulfamethoxazole per kilogram of body weight per day in healthy volunteers. / Stevens, R. C.; Laizure, Steven; Sanders, P. L.; Stein, D. S.

In: Antimicrobial Agents and Chemotherapy, Vol. 37, No. 3, 01.01.1993, p. 448-452.

Research output: Contribution to journalArticle

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