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 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.