Abstract:
:Thiopurines such as azathioprine, 6-mercaptopurine and 6-thioguanine are antimetabolites that have been used for several decades in the treatment of several diseases including inflammatory bowel diseases. Additional anti-inflammatory properties of these thiopurines have been discovered in recent years. Thiopurine metabolism is complex due to the involvement of multiple enzymes, of which the activities are genetically determined and cell type dependent. Single nucleotide polymorphisms in the genes encoding these enzymes have been correlated with altered activities and drug intolerance. Detailed implications of these will be reviewed. Over the years several methods of therapeutic drug monitoring have been developed in an attempt to relate thiopurine drug availability with efficacy and intolerance. In this respect, monitoring pharmacologically active 6-thioguanine nucleotide concentrations is most widely used. So far, however, the clinical usefulness of these methods is hampered by methodological limitations. Some drug interactions may optimize the metabolization of thiopurines and consequently increase its efficacy and decrease drug intolerance. This review focuses on the clinical relevance and usefulness of therapeutic drug monitoring of thiopurines and provides suggestions to optimize thiopurine therapy in the treatment of inflammatory bowel diseases.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Van Asseldonk DP,de Boer NK,Peters GJ,Veldkamp AI,Mulder CJ,Van Bodegraven AAdoi
10.2174/138920009790711887subject
Has Abstractpub_date
2009-11-01 00:00:00pages
981-97issue
9eissn
1389-2002issn
1875-5453journal_volume
10pub_type
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