title: Monitoring thiopurine metabolites in korean pediatric patients with inflammatory bowel disease.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. i101016@skku.edu.
authors.forename: Yon Ho
authors.initials: YH
authors.lastname: Choe
mesh_terms: D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D056910:Republic of Korea; D012307:Risk Factors; D013873:Thionucleotides / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine
keywords: 6-thioguanine nucleotide; Inflammatory bowel disease; azathioprine; thiopurine S-methyltransferase