Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions.
OBJECTIVE
To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS).


METHODS
Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS.


METHODS
County hospital and AIDS clinic.


METHODS
Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole.


METHODS
Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days.


RESULTS
Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 micrograms/mL; P less than 0.05). Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 micrograms/mL; P less than 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%).


CONCLUSIONS
A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.
Lee
B L
BL
San Francisco General Hospital Medical Center, California.
Medina
I
I
Benowitz
N L
NL
Jacob
P
P
Wofsy
C B
CB
Mills
J
J
D000107:Acetylation; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D003622:Dapsone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D011897:Random Allocation; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D014295:Trimethoprim / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*
D003622:Dapsone; D014295:Trimethoprim; D013420:Sulfamethoxazole