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.


METHODS
Trimethoprim-sulfamethoxazole steady-state plasma concentrations were 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 microg/ml, the doses were adjusted if trimethoprim levels were found to be outside this range.


RESULTS
Mean concentrations were 6.7+/-3.3 g/ml for trimethoprim and 187+/-56 microg/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plasma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trimethoprim plasma levels. Adverse reactions associated with co-trimoxazole occurred during 65% of treatment periods and increased with increasing trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one patient. Overall mortality was 2.7%


CONCLUSIONS
Monitoring of co-trimoxazole 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 chronic liver disease or renal failure.
Klinker
H
H
Klinikum der Universität, Medizinische Klinik, Schwerpunkt Hepatologie/Infektiologie, Würzburg, Germany.
Langmann
P
P
Zilly
M
M
Richter
E
E
D017088:AIDS-Related Opportunistic Infections / Q000097:blood* / Q000188:drug therapy*; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007668:Kidney / Q000502:physiology; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000097:blood* / Q000188:drug therapy*; D011446:Prospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination