Molecular diagnosis of thiopurine Smethyltransferase deficiency: genetic basis for azathioprine and mercaptopurine
As expected, a mercaptopurine
treatment of infected rats either untreated or treated with Cy significantly inhibited [alpha]2M synthesis, showing a maximal [alpha]2M level of 182 [micro]g/ ml (Cy untreated) and 231 [micro]g/ml (Cy treated), on the second and the fourth day post-infection, respectively (Fig.
Thiopurine methyltransferase (TPMT) is a cytosolic enzyme that catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including mercaptopurine
(MP), thioguanine (TG), and azathioprine (AZA) (1).
In addition to the anabolic pathway, 6-MP is catabolized to 6-thiouric acid by xanthine oxidase and to 6-methyl mercaptopurine
(6-MMP) by thiopurine S-methyltransferase (TPMT) (8).
It has introduced mercaptopurine
tablets USP, 50 mg.
Thiopurine drugs including azathioprine, mercaptopurine
and thioguanine suppress the immune system and are used in a range of diseases such as lymphoma and leukemia, psoriasis, severe eczema and inflammatory bowel disease.
16 August 2011 - US specialty pharmaceutical and diagnostics company Prometheus Laboratories Inc and US-based Medco Research Institute LLC said yesterday that they have entered into a collaboration to evaluate the use of Prometheus' Thiopurine Metabolite (PTM) testing for optimising dosing of six mercaptopurine
(6MP) or azathioprine (Aza) in patients with inflammatory bowel disease (IBD).
Preponderance of thiopurine Smethyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine
Differing contribution of thiopurine methyltransferase to mercaptopurine
versus thioguanine effects in human leukemic cells.
Use with caution with azathioprine, mercaptopurine
, and warfarin: Coadministration can heighten anticoagulation level.
De novo purine synthesis inhibition and antileukemic effects of mercaptopurine
alone or in combination with methotrexate in vivo.
TPMT is an enzyme known to be involved specifically in the metabolism of mercaptopurine
, which is commonly used for childhood acute lymphoblastic leukemia, and the immunosuppressant azathioprine (Imuran).
The spectrum of thiopurine metabolites that can be measured by our assay methodology (thioguanine, 8-hydroxymercaptopurine, mercaptopurine
, 8hydroxythioguanine, thioxanthine, and thiouric acid plus methylthioguanine and the methyhnercaptopurine metabolites) are safe from oxidation and stable for several days when back-extracted or reconstituted in 0.1 mol/L HCl.
Vinblastine plus etoposide, prednisone, and mercaptopurine
is more effective than monotherapy.