Thioguanine derivatives, azathioprine and 6-mercaptopurine, represent major drugs in the treatment of chronic active inflammatory bowel disease. They are effective in two-thirds of the patients and safe over the long term in patients who can tolerate them (80-90%). Recent progress in understanding the metabolism of these drugs and its implication in clinical practice have brought up new tools a...

BACKGROUND AND AIMS High concentrations of methylated thiopurine metabolites, such as 6-methyl mercaptopurine, are associated with hepatotoxicity during administration of the conventional thiopurines azathioprine or 6-mercaptopurine in IBD patients. Metabolization of the non-conventional thiopurine 6-thioguanine does not generate 6-methyl mercaptopurine. Hence, the aim of our study was to evalu...

BACKGROUND The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently. AIM To study combination of allopurinol with reduced-dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD. METHODS Patients with drug reactions to full-dose thiopurines wer...

In 1995 a report in the New England Journal of Medicine on medication use and risk of Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN) identified carbamazepine as a drug with a higher excess risk than most other drugs known to be associated with this severe muco-cutaneous drug reaction. Since then, pharmacogenomics (the study of the role of inherited and acquired genetic variation...

The administration of the convulsant, L-methionine-dl-sulfoximine (MSO), increased histamine N-methyl transferase (E.C. 2.1.1.8) (HMT) activity in rat and mouse brain and, to a lesser extent, catechol-O-methyl transferase (E.C. 2.1.1.6) (COMT) activity in rat brain. The duration of this effect was shortened by co-administration of L-methionine. The increased HMT activity was seen in S or 7 rat ...

The thiopurines, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are used in the treatment of leukemia. Incorporation of deoxythioguanosine nucleotides (dG(s)) into the DNA of thiopurine-treated cells causes cell death, but there is also evidence that thiopurine metabolites, particularly the 6-MP metabolite methylthioinosine monophosphate (MeTIMP), inhibit de novo purine synthesis (DNPS). The...