Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients.

Abstract

Xanthine oxidase (XO) competes with thiopurine S-methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6-mercaptopurine (6-MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine-induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6-MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu-like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu-like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine-induced toxicity.

• Authors: Liang Ding, Fang-Bin Zhang, Hui Liu, Xiang Gao, Hui-Chang Bi, Ling Huang, Xue-Ding Wang, Bai-Li Chen, Yu Zhang, Chuanzhu Lv, Pin-Jin Hu, Min Huang
• Journal: Pharmacology research & perspectives (Pharmacol Res Perspect) Vol. 9 Issue 3 Pg. e00764 (05 2021) ISSN: 2052-1707 [Electronic] United States
• PMID: 33929082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Chemical References

• Immunosuppressive Agents
• Mercaptopurine
• Xanthine Oxidase
• Azathioprine

Topics

• Adolescent
• Adult
• Aged
• Asian People
• Azathioprine (adverse effects, pharmacology, therapeutic use)
• Child
• Child, Preschool
• Female
• Humans
• Immunosuppressive Agents (adverse effects, pharmacology, therapeutic use)
• Inflammatory Bowel Diseases (blood, drug therapy)
• Leukopenia (chemically induced)
• Male
• Mercaptopurine (adverse effects, pharmacology, therapeutic use)
• Middle Aged
• Retrospective Studies
• Xanthine Oxidase (blood)
• Young Adult