PMID- 33929082
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20221207
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 9
IP  - 3
DP  - 2021 May
TI  - Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel 
      disease patients.
PG  - e00764
LID - 10.1002/prp2.764 [doi]
LID - e00764
AB  - 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.
CI  - (c) 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley 
      & Sons Ltd, British Pharmacological Society and American Society for Pharmacology 
      and Experimental Therapeutics.
FAU - Ding, Liang
AU  - Ding L
AUID- ORCID: 0000-0001-8144-8779
AD  - Clinical Trial and Research Center, People's Hospital of Baoan Shenzhen, 
      Shenzhen, PR China.
FAU - Zhang, Fang-Bin
AU  - Zhang FB
AD  - Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, PR China.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Pharmacy, The First Affiliated Hospital of Jinan University, 
      Guangzhou, PR China.
FAU - Gao, Xiang
AU  - Gao X
AD  - Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Bi, Hui-Chang
AU  - Bi HC
AD  - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun 
      Yat-sen University, Guangzhou, PR China.
FAU - Huang, Ling
AU  - Huang L
AD  - Key Laboratory of Emergency and Trauma, Ministry of Education, College of 
      Emergency and Trauma, Hainan Medical University, Haikou, China.
FAU - Wang, Xue-Ding
AU  - Wang XD
AD  - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun 
      Yat-sen University, Guangzhou, PR China.
FAU - Chen, Bai-Li
AU  - Chen BL
AD  - Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun 
      Yat-sen University, Guangzhou, PR China.
FAU - Lv, Chuanzhu
AU  - Lv C
AUID- ORCID: 0000-0003-3898-583X
AD  - Key Laboratory of Emergency and Trauma, Ministry of Education, College of 
      Emergency and Trauma, Hainan Medical University, Haikou, China.
FAU - Hu, Pin-Jin
AU  - Hu PJ
AD  - Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen 
      University, Guangzhou, PR China.
FAU - Huang, Min
AU  - Huang M
AD  - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun 
      Yat-sen University, Guangzhou, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
RN  - 0 (Immunosuppressive Agents)
RN  - E7WED276I5 (Mercaptopurine)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Asian People
MH  - Azathioprine/*adverse effects/pharmacology/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects/pharmacology/therapeutic use
MH  - Inflammatory Bowel Diseases/*blood/drug therapy
MH  - Leukopenia/chemically induced
MH  - Male
MH  - Mercaptopurine/*adverse effects/pharmacology/therapeutic use
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Xanthine Oxidase/*blood
MH  - Young Adult
PMC - PMC8085934
OTO - NOTNLM
OT  - 6-mercaptopurine
OT  - AZA thioprine
OT  - inflammatory bowel disease
OT  - xanthine oxidase
COIS- All authors have no financial disclosures or conflicts of interest to declare.
EDAT- 2021/05/01 06:00
MHDA- 2022/02/01 06:00
PMCR- 2021/04/30
CRDT- 2021/04/30 08:56
PHST- 2020/10/27 00:00 [received]
PHST- 2021/03/14 00:00 [accepted]
PHST- 2021/04/30 08:56 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/04/30 00:00 [pmc-release]
AID - PRP2764 [pii]
AID - 10.1002/prp2.764 [doi]
PST - ppublish
SO  - Pharmacol Res Perspect. 2021 May;9(3):e00764. doi: 10.1002/prp2.764.