PMID- 28489727
OWN - NLM
STAT- MEDLINE
DCOM- 20180416
LR  - 20181113
IS  - 1536-3694 (Electronic)
IS  - 0163-4356 (Print)
IS  - 0163-4356 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Aug
TI  - Pharmacology of Thiopurine Therapy in Inflammatory Bowel Disease and Complete 
      Blood Cell Count Outcomes: A 5-Year Database Study.
PG  - 399-405
LID - 10.1097/FTD.0000000000000414 [doi]
AB  - BACKGROUND: Thiopurines are the prerequisite for immunomodulation in inflammatory 
      bowel disease (IBD) therapy. When administered in high (oncological) dose, 
      thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and 
      myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted 
      to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the 
      most common adverse events of thiopurines. The aim of this study was to assess 
      the effect of thiopurine metabolites on hematologic and hepatic parameters and to 
      determine which patient characteristics are related to generation of thiopurine 
      metabolites. METHODS: The authors scrutinized the therapeutic drug monitoring 
      database of the VU University medical center and subsequently merged this 
      database with the Clinical Laboratory database of our hospital covering the same 
      time period (2010-2015). RESULTS: The authors included 940 laboratory findings of 
      424 unique patients in this study. Concentrations of 6-thioguanine nucleotides 
      (6-TGN) correlated negatively with red blood cell count, white blood cell count, 
      and neutrophil count in both azathioprine (AZA) and mercaptopurine users. There 
      was a positive correlation with mean corpuscular volume. In patients using 
      6-thioguanine, 6-TGN concentrations correlated positively with white blood cell 
      count. Furthermore, there was an inverse correlation between patient's age and 
      6-TGN concentrations in patients using AZA or 6-thioguanine, and we observed an 
      inverse correlation between body mass index and 6-TGN concentrations in patients 
      using AZA or mercaptopurine. No relations were observed with liver test 
      abnormalities. CONCLUSIONS: Thiopurine derivative therapy influenced bone marrow 
      production and the size of red blood cells. Age and body mass index were 
      important pharmacokinetic factors in the generation of 6-TGN.
FAU - Meijer, Berrie
AU  - Meijer B
AD  - Departments of *Gastroenterology and Hepatology and daggerClinical Pharmacy, VU 
      University Medical Center, Amsterdam; and double daggerDepartment of Gastroenterology, 
      Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical 
      Center, Heerlen-Sittard-Geleen, the Netherlands.
FAU - Wilhelm, Abraham J
AU  - Wilhelm AJ
FAU - Mulder, Chris J J
AU  - Mulder CJJ
FAU - Bouma, Gerd
AU  - Bouma G
FAU - van Bodegraven, Adriaan A
AU  - van Bodegraven AA
FAU - de Boer, Nanne K H
AU  - de Boer NKH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Thionucleotides)
RN  - 0 (azathiopurine)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - E7WED276I5 (Mercaptopurine)
SB  - IM
MH  - Adult
MH  - Blood Cell Count/methods/trends
MH  - Databases, Factual/*trends
MH  - Drug Monitoring/methods/trends
MH  - Female
MH  - Guanine Nucleotides/*blood
MH  - Humans
MH  - Inflammatory Bowel Diseases/*blood/diagnosis/*drug therapy
MH  - Male
MH  - Mercaptopurine/analogs & derivatives/blood/therapeutic use
MH  - Middle Aged
MH  - Thionucleotides/*blood
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC5538301
COIS- The authors declare no conflict of interest.
EDAT- 2017/05/11 06:00
MHDA- 2018/04/17 06:00
PMCR- 2017/08/01
CRDT- 2017/05/11 06:00
PHST- 2017/05/11 06:00 [pubmed]
PHST- 2018/04/17 06:00 [medline]
PHST- 2017/05/11 06:00 [entrez]
PHST- 2017/08/01 00:00 [pmc-release]
AID - TDM17-021-Oe [pii]
AID - 10.1097/FTD.0000000000000414 [doi]
PST - ppublish
SO  - Ther Drug Monit. 2017 Aug;39(4):399-405. doi: 10.1097/FTD.0000000000000414.