Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (~3-14% ...

Thiopurines, Photolysis, Photooxygenation, Purine Derivatives Irradiation (A > 290 nm) of 6-thiopurine and some 9-substituted 6-thiopurines in oxygen saturated iertf-butanol leads to hypoxanthine, purine and purine-6-sulfonic acid or their substituted derivatives. Purine and hypoxanthine formation can be sensitized with dyes. The reaction of 6-thiopurine with singlet oxygen has also been perfor...

Monitoring of thiopurine metabolites is important due to a complex metabolism with large interindividual variation, but the suitability of currently used methods has been questioned. The drawbacks include poor reproducibility, the inability to differentiate between the different analytes, as well as the use of a nontarget matrix. Further research should be directed toward measuring thiopurine m...

The thiopurines azathioprine, mercaptopurine, and thioguanine are prodrugs that are converted to active thioguanine nucleotide metabolites or methylated by thiopurine methyltransferase (TPMT) to compounds with less pharmacologic activity. In the absence of TPMT activity, patients are likely to have higher concentrations of thioguanine nucleotides, which can pose an increased risk of severe life...

Anti-tumor necrosis factor alpha therapy is known as a risk factor of non-tuberculous mycobacteria (NTM) infection. However, there are few reports of NTM infection under treatment with thiopurine agents. We herein report a first case of pulmonary infection caused by Mycobacterium avium complex (MAC) in a patient with Crohn's disease under treatment with thiopurine. After starting antibiotics th...

An improved method is described for the separation of 22 compounds normally related to purine and 6-thiopurine metabolism in biological materials using high-pressure liquid cation-exchange chromatography on strongly acidic exchange resin. The column (0.8 X 100 cm) is eluted with 0.4 M ammonium formate, pH 4.6, at a linear flow velocity of 5.2 cm.min--1 at 50 degrees C. The elution volumes of su...

With great interest we read the article by Kaskas et al (Gut 2003;52:140–2) about safe treatment of thiopurine S-methyltransferase (TPMT) deficient Crohn’s disease patients with azathioprine (AZA). In this paper it is illustrated that TPMT-deficient patients can be successfully treated with very low doses of AZA (,10% of standard initial dose). Unfortunately, this is not the case for all homozy...

In recent years there has been an evolution in the systemic therapy of skin disease, in particular immunosuppressive agents, retinoids and, most lately, biological drugs and new classes of drugs for advanced skin cancer. Developments in drug monitoring include measurement of thiopurine methyl transferase enzyme activity before prescribing azathioprine, to screen for patients at risk of severe b...