VARIABILITY OF SERUM CONCENTRATIONS OF TRIMETHOPRIM AND SULFAMETHOXAZOLE DURING HIGH-DOSE THERAPY

Serum kinetics of trimethoprim and sulfamethoxazole were studied in 23 patients during oral and i.v. treatment of Pneumocystis carinii pneum onia. Daily doses of 15-22 mg/kg trimethoprim and 75-1 10 mg/kg sulfam ethoxazole were given every 6 h. Despite administration of a loading d ose of twice the regular dose, serum trough concentrations continuousl y rose from 12 h to 96 h by 63% for trimethoprim and 102% for sulfamet hoxazole. After 4-6 days mean trough concentrations of trimethoprim an d sulfamethoxazole were 7.7 +/- 3.0 and 198 +/- 74 mg/l, with individu al 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 seru m levels. However, large inter-individual variability was observed des pite weight-specific dosing. Administration of a loading dose did not prevent accumulation of serum levels of trimethoprim and sulfamethoxaz ole over several days of treatment.