title: Variability of serum concentrations of trimethoprim and sulfamethoxazole during high dose therapy.
abstract: Serum kinetics of trimethoprim and sulfamethoxazole were studied in 23 patients during oral and i.v. treatment of Pneumocystis carinii pneumonia. Daily doses of 15-22 mg/kg trimethoprim and 75-110 mg/kg sulfamethoxazole were given every 6 h. Despite administration of a loading dose of twice the regular dose, serum trough concentrations continuously rose from 12 h to 96 h by 63% for trimethoprim and 102% for sulfamethoxazole. After 4-6 days mean trough concentrations of trimethoprim and sulfamethoxazole were 7.7 +/- 3.0 and 198 +/- 74 mg/l, with individual values of < 4.6 and < 103 mg/l in two patients and > 11.4 and > 307 mg/l in two others. Patients treated orally or i.v. had similar serum levels. However, large interindividual variability was observed despite weight-specific dosing. Administration of a loading dose did not prevent accumulation of serum levels of trimethoprim and sulfamethoxazole over several days of treatment.
authors.affiliation: Departement für Innere Medizin, Universitätsspital Zürich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Blaser
authors.forename: B
authors.initials: B
authors.lastname: Joos
authors.forename: M
authors.initials: M
authors.lastname: Opravil
authors.forename: R
authors.initials: R
authors.lastname: Lüthy
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D011446:Prospective Studies; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D014295:Trimethoprim / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: C021282:N(4)-acetylsulfamethoxazole; D014295:Trimethoprim; D003404:Creatinine; D013420:Sulfamethoxazole