DRUG-MONITORING DURING THE TREATMENT OF AIDS-ASSOCIATED PNEUMOCYSTIS-CARINII PNEUMONIA WITH TRIMETHOPRIM-SULFAMETHOXAZOLE

Objective: To monitor trimethoprim and sulfamethoxazole plasma levels in patients with AIDS-associated Pneumocystis carinii pneumonia. Metho d: Trimethoprim-sulfamethoxazole steady-state plasma concentrations we re measured by high-pressure liquid chromatography during 37 episodes of Pneumocystis carinii pneumonia in patients with AIDS. Initially, 15 -23 mg/kg/day trimethoprim and 75-115 mg/kg/day sulfamethoxazole were given i.v. Assuming a therapeutic range for trimethoprim from 4 to 10 mu g/ml, the doses were adjusted if trimethoprim levels were found to be outside this range. Results: Mean concentrations were 6.7 +/- 3.3 m u g/ml for trimethoprim and 187 +/- 56 mu g/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plas ma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trime thoprim plasma levels. Adverse reactions associated with co-trimoxazol e occurred during 65% of treatment periods and increased with increasi ng trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one p atient. Overall mortality was 2.7%. Conclusion: Monitoring of co-trimo xazole levels during the treatment of P. carinii pneumonia in AIDS may help in reducing the high variability of plasma-concentrations and in avoiding severe side-effects especially associated in patients with c hronic liver disease or renal failure.