Document Detail


Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions.
MedLine Citation:
PMID:  2784648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
STUDY OBJECTIVE: To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: 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. SETTING: County hospital and AIDS clinic. PATIENTS: Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. INTERVENTION: Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days. MEASUREMENTS AND MAIN 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.
Authors:
B L Lee; I Medina; N L Benowitz; P Jacob; C B Wofsy; J Mills
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Annals of internal medicine     Volume:  110     ISSN:  0003-4819     ISO Abbreviation:  Ann. Intern. Med.     Publication Date:  1989 Apr 
Date Detail:
Created Date:  1989-04-26     Completed Date:  1989-04-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372351     Medline TA:  Ann Intern Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  606-11     Citation Subset:  AIM; IM; X    
Affiliation:
San Francisco General Hospital Medical Center, California.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Acquired Immunodeficiency Syndrome / complications*
Adult
Dapsone / administration & dosage,  adverse effects,  blood*
Drug Interactions
Drug Therapy, Combination
Female
Humans
Male
Phenotype
Pneumonia, Pneumocystis / drug therapy*,  etiology
Prospective Studies
Random Allocation
Sulfamethoxazole / administration & dosage,  adverse effects,  blood*
Trimethoprim / administration & dosage,  adverse effects,  blood*
Grant Support
ID/Acronym/Agency:
FDR-000137-01-1/FD/FDA HHS; GM-07546/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
723-46-6/Sulfamethoxazole; 738-70-5/Trimethoprim; 80-08-0/Dapsone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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