PMID- 21122571
OWN - NLM
STAT- MEDLINE
DCOM- 20110425
LR  - 20171116
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 4
IP  - 6
DP  - 2010 Dec
TI  - Steady-state of azathioprine during initiation treatment of pediatric 
      inflammatory bowel disease.
PG  - 623-8
LID - 10.1016/j.crohns.2010.06.005 [doi]
AB  - BACKGROUND AND AIM: Azathioprine (AZA) has a slow onset of action in treatment of 
      pediatric inflammatory bowel disease (IBD). It is anticipated, that this delay 
      correlates to the kinetics of 6-thioguanine nucleotides (6-TGN) accumulation. The 
      aim of this study was to evaluate the time to steady state of 6-TGN concentration 
      in red blood cells. METHODS: The inclusion criteria were: a) age 0-19 years b) 
      IBD diagnosis c) AZA treatment initiation. High performance liquid chromatography 
      was used for the 6-TGN analysis. Concentrations of metabolites were studied in 
      weeks 0, 1, 2, 5, and 8 after beginning of treatment. RESULTS: The inclusion 
      criteria were matched to 18 patients with IBD. The median time to steady state of 
      6-TGN was 55.3 days. The mean 6-TGN concentration at the steady state achieved 
      326 (SD 154) pmol/8.108 erythrocytes. High erythrocyte TPMT activity corresponds 
      to the low steady state 6-TGN concentration and vice versa. This correlation 
      reached statistical significance (p<0.01) for the dose expressed in mg per square 
      meter of body surface area. CONCLUSION: The time to steady state of 6-TGN 
      erythrocyte concentration is significantly shorter than would expected according 
      to clinical observation describe earlier.
CI  - Copyright (c) 2010. Published by Elsevier B.V.
FAU - Pozler, O
AU  - Pozler O
AD  - Dept. of Pediatrics, Charles University in Prague, Faculty of Medicine and 
      University Hospital in Hradec Kralove, Czech Republic. pozler@lfhk.cuni.cz
FAU - Chladek, J
AU  - Chladek J
FAU - Maly, J
AU  - Maly J
FAU - Hroch, M
AU  - Hroch M
FAU - Dedek, P
AU  - Dedek P
FAU - Beranek, M
AU  - Beranek M
FAU - Krasnicanova, P
AU  - Krasnicanova P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100824
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.67 (thiopurine methyltransferase)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adolescent
MH  - Azathioprine/*metabolism/*pharmacokinetics/therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Genotype
MH  - Guanine Nucleotides/blood/*pharmacokinetics
MH  - Humans
MH  - Immunosuppressive Agents/*metabolism/*pharmacokinetics/therapeutic use
MH  - Inflammatory Bowel Diseases/*drug therapy/enzymology
MH  - Male
MH  - Mercaptopurine/*analogs & derivatives/blood/metabolism/pharmacokinetics
MH  - Methyltransferases/genetics/metabolism
MH  - Prospective Studies
MH  - Severity of Illness Index
MH  - Thionucleotides/blood/*pharmacokinetics
MH  - Treatment Outcome
EDAT- 2010/12/03 06:00
MHDA- 2011/04/26 06:00
CRDT- 2010/12/03 06:00
PHST- 2010/03/28 00:00 [received]
PHST- 2010/06/20 00:00 [revised]
PHST- 2010/06/21 00:00 [accepted]
PHST- 2010/12/03 06:00 [entrez]
PHST- 2010/12/03 06:00 [pubmed]
PHST- 2011/04/26 06:00 [medline]
AID - S1873-9946(10)00095-4 [pii]
AID - 10.1016/j.crohns.2010.06.005 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2010 Dec;4(6):623-8. doi: 10.1016/j.crohns.2010.06.005. Epub 
      2010 Aug 24.