PMID- 22398098
OWN - NLM
STAT- MEDLINE
DCOM- 20130114
LR  - 20220330
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 6
IP  - 6
DP  - 2012 Jul
TI  - Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine 
      tolerant IBD patients on maintenance therapy.
PG  - 698-707
LID - 10.1016/j.crohns.2011.12.003 [doi]
AB  - BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of 
      thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed 
      therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is 
      >/=235 pmol/8x10(8) erythrocytes. The aim of this prospective cross-sectional study 
      was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an 
      exacerbation with those in remission, and to determine the therapeutic 6-TGN 
      cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were 
      thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, 
      CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one 
      patients had an exacerbation, 59 patients were in remission. In 17% of all 
      patients 6-TGN levels were compatible with non-compliance. The median 6-TGN 
      levels were not significantly different between the exacerbation and remission 
      group (227 versus 263 pmol/8x10(8) erythrocytes, p=0.29). The previous reported 
      therapeutic 6-TGN cut-off level of 235 pmol/8x10(8) erythrocytes was confirmed in 
      this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN 
      levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission 
      (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active 
      and quiescent disease. 6-TGN levels below or above the therapeutic threshold are 
      associated with a significant higher chance of IBD exacerbation and remission, 
      respectively. These data support the role of therapeutic drug monitoring in 
      thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, 
      and can be used as a practical tool to optimize thiopurine therapy, especially in 
      case of thiopurine non-response.
CI  - Copyright (c) 2011 European Crohn's and Colitis Organisation. Published by Elsevier 
      B.V. All rights reserved.
FAU - Gilissen, Lennard P L
AU  - Gilissen LP
AD  - Department of Gastroenterology and Hepatology, Catharina Hospital, Eindhoven, The 
      Netherlands. lennard.gilissen@cze.nl
FAU - Wong, Dennis R
AU  - Wong DR
FAU - Engels, Leopold G J B
AU  - Engels LG
FAU - Bierau, Jorgen
AU  - Bierau J
FAU - Bakker, Jaap A
AU  - Bakker JA
FAU - Paulussen, Aimee D C
AU  - Paulussen AD
FAU - Romberg-Camps, Marielle J
AU  - Romberg-Camps MJ
FAU - Stronkhorst, Arnold
AU  - Stronkhorst A
FAU - Bus, Paul
AU  - Bus P
FAU - Bos, Laurens P
AU  - Bos LP
FAU - Hooymans, Piet M
AU  - Hooymans PM
FAU - Stockbrugger, Reinhold W
AU  - Stockbrugger RW
FAU - Neef, Cees
AU  - Neef C
FAU - Masclee, Ad A M
AU  - Masclee AA
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
DEP - 20120110
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Biomarkers, Pharmacological)
RN  - 0 (Genetic Markers)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 46S541971T (Thioinosine)
RN  - 7021-52-5 (6-methylthiopurine ribonucleoside-5'-phosphate)
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  - Adult
MH  - Aged
MH  - Azathioprine/metabolism/*therapeutic use
MH  - Biomarkers, Pharmacological/blood
MH  - Chromatography, High Pressure Liquid
MH  - Cross-Sectional Studies
MH  - Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - *Drug Monitoring
MH  - Female
MH  - Genetic Markers
MH  - Guanine Nucleotides/*blood
MH  - Humans
MH  - Immunosuppressive Agents/metabolism/*therapeutic use
MH  - Inflammatory Bowel Diseases/*drug therapy/genetics/metabolism
MH  - Maintenance Chemotherapy
MH  - Male
MH  - Medication Adherence/statistics & numerical data
MH  - Mercaptopurine/metabolism/*therapeutic use
MH  - Methyltransferases/genetics/metabolism
MH  - Middle Aged
MH  - Prospective Studies
MH  - Severity of Illness Index
MH  - Thioinosine/*analogs & derivatives/blood
MH  - Thionucleotides/*blood
MH  - Young Adult
EDAT- 2012/03/09 06:00
MHDA- 2013/01/15 06:00
CRDT- 2012/03/09 06:00
PHST- 2011/06/14 00:00 [received]
PHST- 2011/11/28 00:00 [revised]
PHST- 2011/12/05 00:00 [accepted]
PHST- 2012/03/09 06:00 [entrez]
PHST- 2012/03/09 06:00 [pubmed]
PHST- 2013/01/15 06:00 [medline]
AID - S1873-9946(11)00340-0 [pii]
AID - 10.1016/j.crohns.2011.12.003 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2012 Jul;6(6):698-707. doi: 10.1016/j.crohns.2011.12.003. Epub 
      2012 Jan 10.