Document Detail

Evaluation of sulfonamide detoxification pathways in haematologic malignancy patients prior to intermittent trimethoprim-sulfamethoxazole prophylaxis.
MedLine Citation:
PMID:  21204907     Owner:  NLM     Status:  MEDLINE    
AIMS: Patients with haematologic malignancies have a reportedly high incidence of sulfamethoxazole (SMX) hypersensitivity. The objective of this study was to determine whether deficiencies in sulfonamide detoxification pathways, to include glutathione (GSH) and ascorbate (AA), and cytochrome b(5) (b5) and cytochrome b(5) reductase (b5R), were prevalent in these patients. A secondary pilot objective was to determine whether the incidence of drug hypersensitivity following intermittent trimethoprim-SMX (TMP-SMX) prophylaxis approached that reported for high dose daily regimens.
METHODS: Forty adult patients with haematologic malignancies (HM) and 35 healthy adults were studied; an additional 13 HM patients taking ascorbate supplements (HM-AA) were also evaluated. Twenty-two of 40 HM patients were prescribed and were compliant with TMP-SMX 960 mg three to four times weekly.
RESULTS: There were no significant differences between HM and healthy groups in plasma AA (median 37.2 µm vs. 33.9 µm) or red blood cell GSH (1.9 mmvs. 1.8 mm). However, plasma AA was correlated significantly with leucocyte b5/b5R reduction (r= 0.39, P= 0.002). Deficient b5/b5R activities were not found in HM patients. In fact, patients with chronic lymphocytic leukaemia or myeloma had significantly higher median activities (80.7 µmol mg(-1) min(-1)) than controls (18.9 µmol mg(-1) min(-1), P= 0.008). After 3-4 weeks of treatment, no patients developed SMX-specific T cells and only one patient developed rash.
CONCLUSIONS: Deficiencies of blood antioxidants and b5/b5R reduction were not found in this population with haematologic malignancies, and the development of skin rash and drug-specific T cells appeared to be uncommon with intermittent TMP-SMX prophylaxis.
Mahmoud Abouraya; James C Sacco; Brad S Kahl; Lauren A Trepanier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  71     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-06-21     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  566-74     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706-1102, USA.
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MeSH Terms
Anti-Infective Agents / adverse effects*
Ascorbic Acid / metabolism
Case-Control Studies
Cell Proliferation / drug effects
Cytochrome-B(5) Reductase / metabolism
Dose-Response Relationship, Drug
Drug Hypersensitivity / etiology*
Glutathione / metabolism
Hematologic Neoplasms / drug therapy*
Metabolic Detoxication, Drug
Middle Aged
Statistics as Topic
Sulfamethoxazole / metabolism
Sulfonamides / metabolism*
T-Lymphocytes / drug effects
Trimethoprim-Sulfamethoxazole Combination / adverse effects*
Young Adult
Grant Support
Reg. No./Substance:
0/Anti-Infective Agents; 0/Sulfonamides; 50-81-7/Ascorbic Acid; 70-18-8/Glutathione; 723-46-6/Sulfamethoxazole; 8064-90-2/Trimethoprim-Sulfamethoxazole Combination; EC Reductase

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

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