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• W2541330983 abstract "OBJECTIVES: Thiopurine drugs are the most commonly used steroid-sparing therapies in moderate-to-severe inflammatory bowel disease (IBD). Their complex metabolism and their narrow therapeutic windows means that optimal dosing is difficult. However, weight-based dosing is the norm. Similar antimetabolites are dosed by body composition parameters. In IBD, treatment response and toxicity has been shown to correlate with thiopurine metabolite levels. We sought to determine whether weight or body composition parameters predicted therapeutic 6-thioguanine nucleotide (6TGN) or toxic 6-methylmercaptopurine (6MMP) levels. METHODS: This single-center retrospective cohort study identified 66 IBD patients who had body composition analysis and thiopurine metabolite levels tested. Statistical analysis was performed using Spearman correlation, Kruskal–Wallis, Mann–Whitney, and unpairedttests and receiver-operator operating characteristic curves. APvalue of <0.05 was considered significant. RESULTS: No correlation was identified between 6TGN and any body composition parameters, absolute drug dose or drug dose/kg of fat mass, fat-free mass (FFM), subcutaneous adipose tissue area, or visceral adipose tissue area. However, 6MMP correlated with azathioprine dose, thiopurine dose/kg of body weight, and with several body composition parameters. CONCLUSIONS: No relationship was found between therapeutic metabolite levels and weight or body composition compartments. Higher thiopurine doses, especially in relation to FFM, are associated with higher levels of potentially hepatotoxic 6MMP and shunting toward this metabolite. Conventional weight-based dosing to attain therapeutic metabolite levels appears unreliable and may be replaced by metabolite level testing." @default.
• W2541330983 created "2016-11-04" @default.
• W2541330983 creator A5046704389 @default.
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• W2541330983 date "2016-10-01" @default.
• W2541330983 modified "2023-10-14" @default.
• W2541330983 title "Weight and Body Composition Compartments do Not Predict Therapeutic Thiopurine Metabolite Levels in Inflammatory Bowel Disease" @default.
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• W2541330983 doi "https://doi.org/10.1038/ctg.2016.56" @default.
• W2541330983 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5288590" @default.
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