Affiliation:
1. Department of Clinical Pharmacy, University of Tennessee, Memphis 38163.
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 micrograms/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 less than 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference24 articles.
1. The treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome;Butkus-Small C.;Arch. Intern. Med.,1985
2. Centers for Disease Control. 1989. AIDS Weekly Surveillance Report 30 January 1989 p. 1-5. Centers for Disease Control Atlanta.
3. Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia;Davey R. T.;Antimicrob. Agents Chemother.,1990
4. Similar hematologic changes in children receiving trimethoprim-sulfamethoxazole or amoxicillin for otitis media;Feldman S.;J. Pediatr.,1985
5. Fong I. W. 1988. Program Abstr. 28th Intersci. Conf. Antimicrob. Agents Chemother. abstr. 1226.
Cited by
55 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献