PMID- 29040228
OWN - NLM
STAT- MEDLINE
DCOM- 20180628
LR  - 20181113
IS  - 1536-3694 (Electronic)
IS  - 0163-4356 (Print)
IS  - 0163-4356 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Dec
TI  - Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients 
      With Inflammatory Bowel Disease.
PG  - 584-588
LID - 10.1097/FTD.0000000000000455 [doi]
AB  - The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can 
      be optimized by the application of therapeutic drug monitoring. In this 
      procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) 
      metabolites are monitored and related to therapeutic response and adverse events, 
      respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by 
      several analytical limitations resulting in an impaired translation of metabolite 
      levels to clinical outcome in IBD. Thiopurine metabolism is cell specific and 
      requires nucleated cells and particular enzymes for 6-TGN formation. In the 
      current therapeutic drug monitoring, metabolite levels are assessed in 
      erythrocytes, whereas leukocytes are considered the main target cells of these 
      drugs. Furthermore, currently used methods do not distinguish between active 
      nucleotides and their unwanted residual products. Last, there is a lack of a 
      standardized laboratorial procedure for metabolite assessment regarding the 
      substantial instability of erythrocyte 6-TGN. To improve thiopurine therapy in 
      patients with IBD, it is necessary to understand these limitations and recognize 
      the general misconceptions in this procedure.
FAU - Simsek, Melek
AU  - Simsek M
AD  - *Department of Gastroenterology and Hepatology, VU University Medical Center, 
      Amsterdam; and daggerDepartment of Gastroenterology, Geriatrics, Internal and 
      Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, 
      Heerlen-Sittard-Geleen, the Netherlands.
FAU - Meijer, Berrie
AU  - Meijer B
FAU - Mulder, Chris J J
AU  - Mulder CJJ
FAU - van Bodegraven, Adriaan A
AU  - van Bodegraven AA
FAU - de Boer, Nanne K H
AU  - de Boer NKH
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Antimetabolites)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Antimetabolites/blood/pharmacokinetics/therapeutic use
MH  - Azathioprine/*blood/pharmacokinetics/therapeutic use
MH  - Drug Monitoring/*methods
MH  - Humans
MH  - Inflammatory Bowel Diseases/*drug therapy
MH  - Mercaptopurine/*blood/pharmacokinetics/therapeutic use
MH  - Thioguanine/*blood/pharmacokinetics/therapeutic use
PMC - PMC5690305
COIS- C. J. J. Mulder has served as a consultant and principal investigator for Teva 
      Pharma B.V. A. A. van Bodegraven has served as a consultant or speaker for 
      AbbVie, Ferring, Janssen, MSD, Pfizer, Takeda, TEVA, Tramedico, Vifor, and the 
      Dutch Ministry of Health (ZonMW). He has received (unrestricted) research grants 
      from Aventis and Ferring, and the Dutch Ministry of Health. N. K. H. de Boer has 
      served as a speaker for AbbVie, Takeda, and MSD. He has served as a consultant 
      and principal investigator for Takeda and Teva Pharma B.V. He has received a 
      (unrestricted) research grant from Dr. Falk and Takeda. The remaining authors 
      declare no conflict of interest.
EDAT- 2017/10/19 06:00
MHDA- 2018/06/29 06:00
PMCR- 2017/11/16
CRDT- 2017/10/18 06:00
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2018/06/29 06:00 [medline]
PHST- 2017/10/18 06:00 [entrez]
PHST- 2017/11/16 00:00 [pmc-release]
AID - TDM017-017RA [pii]
AID - 10.1097/FTD.0000000000000455 [doi]
PST - ppublish
SO  - Ther Drug Monit. 2017 Dec;39(6):584-588. doi: 10.1097/FTD.0000000000000455.