| Thiopurine S-methyltransferase as a target for drug interactions. | |
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MedLine Citation:
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PMID: 15952020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The present study was undertaken to investigate the possible effects of various agents on thiopurine methyltransferase (TPMT) activity in red blood cells (RBCs) from patients with chronic inflammatory bowel disease (IBD). METHODS: In three groups of patients with very high, normal and intermediate TPMT activity (each n=6), the inhibitory potential of furosemide, piretanide, azathioprine (AZA) and testosterone was assessed by ex vivo measurements of TPMT activity in RBCs. From individual concentration-response curves, IC50 values have been determined. RESULTS: Independent of the basal TPMT activity, lowest IC50 values were calculated for furosemide (15-19 microM), followed by testosterone (30-72 microM), piretanide (300-313 microM) and AZA (430-532 microM). Compared with reported plasma concentration achieved during treatment, only furosemide would have the potential to inhibit TPMT also in vivo, whereas the IC50 values of the other agents are far above the corresponding plasma levels. CONCLUSIONS: Our ex vivo study revealed that only furosemide has the potential to inhibit TPMT activity in patients with IBD. This possibility should be taken into consideration if the diuretic and AZA or 6-mercaptopurine are coadministered. However, the extrapolation to the clinical setting remains open. |
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Authors:
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Hua-Wen Xin; Christine Fischer; Matthias Schwab; Ulrich Klotz |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-06-11 |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: 61 ISSN: 0031-6970 ISO Abbreviation: Eur. J. Clin. Pharmacol. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-07-26 Completed Date: 2006-09-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 395-8 Citation Subset: IM |
Affiliation:
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Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376, Stuttgart, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Mercaptopurine
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administration & dosage,
pharmacology Adolescent Adult Aged Azathioprine / administration & dosage, pharmacology Child Diuretics / administration & dosage, pharmacology* Dose-Response Relationship, Drug Drug Interactions Erythrocytes / drug effects*, metabolism Female Furosemide / administration & dosage, pharmacology* Humans Immunosuppressive Agents / administration & dosage, pharmacology Inflammatory Bowel Diseases / blood Inhibitory Concentration 50 Male Methyltransferases / antagonists & inhibitors, metabolism* Middle Aged |
| Chemical | |
Reg. No./Substance:
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0/Diuretics; 0/Immunosuppressive Agents; 446-86-6/Azathioprine; 50-44-2/6-Mercaptopurine; 54-31-9/Furosemide; EC 2.1.1.-/Methyltransferases; EC 2.1.1.67/thiopurine methyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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