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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% of the population) show moderate toxicity, and homozygous wild‐type individuals (~86–97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.

Clinical Pharmacology & Therapeutics (2011) 89 3, 387–391. doi:10.1038/clpt.2010.320