Yonsei Med J.  2014 Sep;55(5):1289-1296. 10.3349/ymj.2014.55.5.1289.

Monitoring Thiopurine Metabolites in Korean Pediatric Patients with Inflammatory Bowel Disease

• Kim MJ
• Lee SY
• Choe YH

• KMID: 1799493
• DOI: http://doi.org/10.3349/ymj.2014.55.5.1289

Abstract

PURPOSE
This study aimed to assess the role of thiopurine S-methyltransferase (TPMT) and 6-thioguanine nucleotide (6-TGN) as predictors of clinical response and side effects to azathioprine (AZA), and estimate the optimal AZA dose in Korean pediatric inflammatory bowel disease (IBD) patients.
MATERIALS AND METHODS
One hundred and nine pediatric IBD patients in whom AZA treatment was required were enrolled. Thiopurine metabolites were monitored since September 2010. Among them, 83 patients who had prescribed AZA for at least 3 months prior to September 2010 were enrolled and followed until October 2011 to evaluate optimal AZA dose, adverse effects and disease activity before and after thiopurine metabolite monitoring.
RESULTS
The result of the TPMT genotype was that 102 patients were *1/*1 (wild type), four were *1/*3C, one was *1/*6, one was *1/*16 (heterozygote) and one was *3C/*3C (homozygote). Adverse effects happened in 31 patients pre-metabolite monitoring and in only nine patients post-metabolite monitoring. AZA dose was 1.4+/-0.31 mg/kg/day before monitoring and 1.1+/-0.46 mg/kg/day after monitoring (p<0.001). However, there were no statistical differences in disease activity during metabolite monitoring period (p=0.34). Adverse effects noticeably decreased although reduction of the AZA dose since monitoring.
CONCLUSION
TPMT genotype and thiopurine metabolite monitoring could be helpful to examine TPMT genotypes before administering AZA and to measure 6-TGN concentrations during prescribing AZA in IBD patients.

Keyword

Inflammatory bowel disease; azathioprine; thiopurine S-methyltransferase; 6-thioguanine nucleotide

MeSH Terms

Adolescent
Adult
Azathioprine/*adverse effects/therapeutic use
Child
Child, Preschool
Female
Genotype
Guanine Nucleotides/metabolism
Humans
Inflammatory Bowel Diseases/*drug therapy/metabolism
Male
Methyltransferases/genetics/metabolism
Republic of Korea
Risk Factors
Thionucleotides/metabolism
Treatment Outcome
Azathioprine
Guanine Nucleotides
Methyltransferases
Thionucleotides

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