| Evaluation of sulfonamide detoxification pathways in haematologic malignancy patients prior to intermittent trimethoprim-sulfamethoxazole prophylaxis. | |
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MedLine Citation:
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PMID: 21204907 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mahmoud Abouraya; James C Sacco; Brad S Kahl; Lauren A Trepanier |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: 71 ISSN: 1365-2125 ISO Abbreviation: Br J Clin Pharmacol Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-14 Completed Date: 2011-06-21 Revised Date: 2012-04-02 |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 566-74 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706-1102, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged 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* Female Glutathione / metabolism Hematologic Neoplasms / drug therapy* Humans Male 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 | |
ID/Acronym/Agency:
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R01 GM61753/GM/NIGMS NIH HHS; T32 RR023916/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 1.6.2.2/Cytochrome-B(5) Reductase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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