Thiopurine Dose in Intermediate and Normal Metabolizers of Thiopurine Methyltransferase May Differ Three-Fold Sharon J. Gardiner, Richard B. Gearry,

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Thiopurine Dose in Intermediate and Normal Metabolizers of Thiopurine Methyltransferase May Differ Three-Fold Sharon J. Gardiner, Richard B. Gearry, Evan J. Begg, Mei Zhang, Murray L. Barclay Clinical Gastroenterology and Hepatology Volume 6, Issue 6, Pages 654-660 (June 2008) DOI: 10.1016/j.cgh.2008.02.032 Copyright © 2008 AGA Institute Terms and Conditions

Figure 1 Metabolism of azathioprine and 6-MP. GMPS, guanosine monophosphate synthetase; HGPRT, hypoxanthine guanine phosphoribosyltransferase; IMPDH, inosine monophosphate dehydrogenase; TG, thioguanine; TGMP, thioguanine monophosphate; TGN, thioguanine nucleotides; TIMP, thionosine monophosphate; TXMP, thioxanthosine monophosphate. Clinical Gastroenterology and Hepatology 2008 6, 654-660DOI: (10.1016/j.cgh.2008.02.032) Copyright © 2008 AGA Institute Terms and Conditions

Figure 2 (A) Thiopurine dose (as azathioprine equivalents) in TPMT*1/*1 (Δ) and *1/*3 (○) genotypes and in (B) normal (Δ, ≥9.3 IU/mL) phenotypes and intermediate (○, 5–9.2 IU/mL) and presented as mean and 95% CI. †Groups became significantly different (P < .05). Clinical Gastroenterology and Hepatology 2008 6, 654-660DOI: (10.1016/j.cgh.2008.02.032) Copyright © 2008 AGA Institute Terms and Conditions

Figure 3 TPMT activity versus weight-adjusted thiopurine dose. Clinical Gastroenterology and Hepatology 2008 6, 654-660DOI: (10.1016/j.cgh.2008.02.032) Copyright © 2008 AGA Institute Terms and Conditions

Figure 4 (A) Actual and (B) dose-adjusted 6-TGN concentrations versus TPMT genotype at month 9. Data are presented as mean and 95% CI. Mean actual and dose-adjusted 6-TGN concentrations were 2-fold (P = .016) and 3-fold higher (P = .0007) in the TPMT*1/*3 versus the *1/*1 genotype, respectively. Clinical Gastroenterology and Hepatology 2008 6, 654-660DOI: (10.1016/j.cgh.2008.02.032) Copyright © 2008 AGA Institute Terms and Conditions

Figure 5 Dose-adjusted 6-TGN concentrations versus TPMT activity (includes line of best fit plus 95% CI of this line). Clinical Gastroenterology and Hepatology 2008 6, 654-660DOI: (10.1016/j.cgh.2008.02.032) Copyright © 2008 AGA Institute Terms and Conditions