Although thiopurine S-methyltransferase (TPMT) genotyping to guide thiopurine dosing is common in the pediatric cancer population, limited data exist on TPMT testing implementation in diverse, multidisciplinary settings. We established TPMT testing (genotype and enzyme) with clinical decision support, provider/patient education, and pharmacist consultations in a tertiary medical center and coll...

Inosine triphosphatase (ITPase) is one of the enzymes involved in thiopurine metabolism. Polymorphisms in the ITPA gene, resulting in a decreased activity of ITPase, are associated with adverse drug reactions during thiopurine therapy. Measuring ITPase activity is therefore of utmost importance. We compared measurement of ITPase activity in fresh erythrocyte lysates and eluates of dried blood s...

An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for my...

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The Clinical Pharmacogenomics Service (CPS) at Boston Children’s Hospital (BCH) was established to use genomic information to make pediatric medications safer. Nearly one-quarter of outpatients are prescribed one or more drugs with genetic information in the FDA label [1]. However, there are still important barriers that must be overcome for routine pharmacogenomic (PGx) clinical use: (1) ident...

1. The transport of 6-thioguanine and 6-mercaptopurine has been studied with isolated jejunal loops of mouse small intestine. H.p.l.c. was used to identify and quantify the thiopurines and their metabolites in the serosal secretions. 2. When the lumen of the intestinal loops contained either 6-thioguanine or 6-mercaptopurine at a concentration of 1 mmol/l, the concentration of unmetabolized dru...

A number of phosphinegold(I) thiolates where, generally, the thiolate is derived from a thionucleobase, have been screened for anti-arthritic activity in Dark Agouti rats, a gold sensitive model for arthritis. Potency and toxicity data showed that, generally, the Ph(3)P derivatives and species based on thiopurines were the most effective and that with other complexes enhanced activity was accom...