PMID- 23856979
OWN - NLM
STAT- MEDLINE
DCOM- 20131029
LR  - 20171116
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 53
IP  - 9
DP  - 2013 Sep
TI  - Usefulness of thiopurine metabolites in predicting azathioprine resistance in 
      pediatric IBD patients.
PG  - 900-8
LID - 10.1002/jcph.134 [doi]
AB  - Few data on azathioprine (AZA) therapy for inflammatory bowel disease (IBD) exist 
      for children. We evaluated whether the 6-thioguanine nucleotides (6-TGN) level 
      predicts AZA refractoriness in children with IBD and whether children benefit an 
      AZA dose escalation. Seventy-eight children with IBD initially treated with an 
      AZA dose of 1.5-2.5 mg/kg/day were retrospectively included. The dose was 
      adjusted based on the clinical status. The receiver operating characteristic 
      curve and logistic regression were used to determine predictors for AZA 
      resistance. Initially, 18 of 40 (45%) patients receiving a dose of <2 mg/kg/day 
      and 11 of 38 (28.9%) patients receiving a dose of 2-2.5 mg/kg/day achieved 
      remission. The 6-TGN level above 250 pmol/8.10(8) RBCs was associated with a 
      higher remission rate, though non-significant. Among 35 patients with a dose 
      escalation due to treatment failure, 12 (34.3%) achieved remission (the median 
      6-TGN level increased from 260 to 394 pmol/8.10(8) RBCs [P = .002]), 23 (67.6%) 
      were AZA refractory. A 6-TGN level above 405 pmol/8.10(8) RBCs was the only 
      predictor for AZA resistance (sensitivity 78.3%, specificity 75%, OR 10.8 [95% 
      CI: 2.1-55.7, P = .004]). Serial metabolite monitoring is useful to identify 
      children with IBD resistant to AZA. Children who cannot achieve remission despite 
      a 6-TGN level above 405 pmol/8.10(8) RBCs should receive alternative therapies 
      than dose increase.
CI  - (c) The Author(s) 2013.
FAU - Nguyen, Thi-Van-Anh
AU  - Nguyen TV
AD  - Departement de Pharmacie Clinique, Pharmacocinetique et Evaluation du Medicament 
      EA4169, Universite de Lyon, Lyon 1, ISPB, Lyon, France.
FAU - Nguyen, Thi-Mai-Hoang
AU  - Nguyen TM
FAU - Lachaux, Alain
AU  - Lachaux A
FAU - Boulieu, Roselyne
AU  - Boulieu R
LA  - eng
PT  - Journal Article
DEP - 20130715
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antimetabolites)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adolescent
MH  - Antimetabolites/*pharmacokinetics/therapeutic use
MH  - Azathioprine/*pharmacokinetics/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - *Drug Resistance
MH  - Female
MH  - Humans
MH  - Inflammatory Bowel Diseases/drug therapy/*metabolism
MH  - Leukopenia/chemically induced
MH  - Male
MH  - Mercaptopurine/*analogs & derivatives/metabolism
MH  - Thioguanine/*metabolism
OTO - NOTNLM
OT  - azathioprine
OT  - inflammatory bowel disease
OT  - metabolites
OT  - pediatrics
OT  - resistance
EDAT- 2013/07/17 06:00
MHDA- 2013/10/30 06:00
CRDT- 2013/07/17 06:00
PHST- 2012/10/31 00:00 [received]
PHST- 2013/06/12 00:00 [accepted]
PHST- 2013/07/17 06:00 [entrez]
PHST- 2013/07/17 06:00 [pubmed]
PHST- 2013/10/30 06:00 [medline]
AID - 10.1002/jcph.134 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2013 Sep;53(9):900-8. doi: 10.1002/jcph.134. Epub 2013 Jul 15.