Thiopurine methyltransferase (TPM T) 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 wildtype 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.

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samples 33 PCD, RK, SM, VN and DS guided experimental design and analysis. 34 MW converted the data in GNPS, developed spectral search and molecular explorer. 35 TT, VN and SM raised animals and guided experimental design. 36 RQ and PD wrote the manuscript 37 38Abstract 39 A mosaic of cross-phyla chemical interactions occurs between all metazoans and their 40 microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, 41 particularly those with a mucosal surface, associate with highly adapted and evolved 42 microbial consortia 1 . The microbial residents within these organ systems are increasingly well 43 characterized, yielding a good understanding of human microbiome composition, but we have 44 yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth 45 of the chemical diversity it contributes 2 . A number of molecular families are known to be 46 shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid 47 values of the two data types onto the murine 3-D model showed how the gut samples were monosaccharides in all regions of the GI tract, which were absent in SPF animals. Instead, a 132

The drugs that are effective in inflammatory bowel disease (IBD) act by inhibiting the chronic unregulated intestinal inflammation in these patients. The mainstays of the drug therapy of IBD are a variety of formulations of 5-aminosalicylic acid (5-ASA), the conventional and newer low bioavailability glucocorticoids, the nitroimidazole antibiotic metronidazole, and certain immunomodulating agents. Increased understanding of the mechanisms of inflammation in IBD has permitted the development of effective designer drugs. These agents are products of the biotechnology industry and include antibodies to tumor necrosis factor (TNF)-alpha, antisense oligonucleotides and recombinant human interleukin (IL)-10. In addition, a number of other agents such as nicotine and n-3 fatty acids are useful in certain patients. This review first focuses on the pharmacology and mechanism of action of these drugs in IBD, followed by an approach to the treatment of patients with ulcerative colitis (UC) and Crohns disease (CD). The recommendations consider type and activity of IBD and are based largely on data from controlled trials and systematic reviews in the IBD literature.

Linked ContentThis article is linked to Singh et al and Murray papers. To view these articles, visit https://doi.org/10.1111/apt.15214 and https://doi.org/10.1111/apt.15259.