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Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6‐mercaptopurine and azathioprine.
Open accessAbstract
Thiopurine drugs are used in the treatment of inflammatory bowel disease—as are sulphasalazine and its metabolite 5‐aminosalicylic acid (ASA). S‐Methylation catalyzed by thiopurine methyltransferase (TPMT) is a major pathway in the metabolism of thiopurines. The hypothesis was tested that TPMT might be inhibited by sulphasalazine or isomers of ASA. Sulphasalazine as well as 3‐, 4‐ and 5‐ASA inhibited recombinant human TPMT, with IC50 values of 78, 99, 2600 and 1240 microM, respectively. Kinetic studies demonstrated that the inhibition of TPMT by sulphasalazine and ASA isomers was non‐competitive with regard to the thiopurine substrate, 6‐MP, and was uncompetitive with regard to the methyl donor for the reaction, S‐adenosyl‐L‐methionine. Our observations raise the possibility of a clinically significant drug‐ drug interaction in patients treated simultaneously with sulphasalazine and thiopurine drugs.
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Cited by
Weinshilboum, R. M., Otterness, D. M., & Szumlanski, C. L. (1999) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.39.1.19 · Cited by 549
Self-citationLichtenstein, G. R., Abreu, M. T., Cohen, R., & Tremaine, W. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.01.048 · Cited by 417
Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice
Gardiner, S. J., & Begg, E. J. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.6 · Cited by 406
Turner, D., Levine, A., Escher, J. C., Griffiths, A. M., Russell, R. K., Dignass, A., Dias, J. A., Bronsky, J., Braegger, C. P., Cucchiara, S., et al. (2012) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e3182662233 · Cited by 382
Systematic review with meta-analysis: inflammatory bowel disease in the elderly
Gisbert, J. P., & Chaparro, M. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12616 · Cited by 158
Metadata
- Authors
- Szumlanski, C., & Weinshilboum, R.
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 1995-04
- Volume
- 39
- Issue
- 4
- Pages
- 456-459
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- OpenAlex
- W2040894582
- Cited by
- 223
- References
- 0
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Szumlanski, C., & Weinshilboum, R. (1995). Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6‐mercaptopurine and azathioprine. British Journal of Clinical Pharmacology. https://doi.org/10.1111/j.1365-2125.1995.tb04478.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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