therapy for psoriasis causing toxic hepatic venoocclusive disease.
6-MP is converted nonenzymatically to 6-thioguanine
(6-TGN), the biologically active metabolite responsible for the therapeutic response.
A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising: (a) administering a drug providing 6-thioguanine
to a subject having said immune-mediated gastrointestinal disorder; and (b) determining the level of 6-thioguanine
in said subject having said immune-mediated gastrointestinal disorder, wherein the level of 6-thioguanine
less than about 230 pmol per 8x[10.
nucleotide-adapted azathioprine therapy does not lead to higher remission rates than standard therapy in chronic active Crohn disease: results from a randomized, controlled, open trial.
Utilisation of erythrocyte 6-thioguanine
metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease.
It's unnecessary to routinely monitor 6-thioguanine
nucleotide (6-TGN), the active metabolite of azathioprine and 6-MP.
TPMT assay methodology is poorly standardized, but our results should apply equally to the respective cutoff activities of other assays; for example, when 6-thioguanine
is used as substrate.
6-MP is activated to 6-thioinosine monophosphate (6-TIMP) and subsequently to 6-thioguanine
(6-TG) nucleotides (6-TGNs) by a multistep process involving several enzymes of the purine salvage pathway (2).
Reagents and media for cell culture were obtained from the following suppliers: 6-thioguanine
(TG), citric acid, and dimethyl sulfoxide (DMSO) were obtained from Sigma (St.
Although the physiologic function of the enzyme is still unknown, TPMT is involved in the metabolism of the thiopurine drugs 6-mercaptopurine, 6-thioguanine
, and azathioprine.
The thiopurines 6-mercaptopurine (Purinethol[R]), azathioprine (Imurel[R]), and 6-thioguanine
(Lanvis[R]) are used in the treatment of leukemia and inflammatory bowel disease (IBD) (4) and to prevent organ transplant rejection (1-3).
The enzyme catalyzes the S-methylation of these medicinal agents, a metabolic pathway that competes with the formation of pharmacologically active 6-thioguanine
nucleotides (6-TGNs), thereby modulating their therapeutic and toxic effects (1,2).