PMID- 27787512
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2155-384X (Print)
IS  - 2155-384X (Electronic)
IS  - 2155-384X (Linking)
VI  - 7
IP  - 10
DP  - 2016 Oct 27
TI  - Weight and Body Composition Compartments do Not Predict Therapeutic Thiopurine 
      Metabolite Levels in Inflammatory Bowel Disease.
PG  - e199
LID - 10.1038/ctg.2016.56 [doi]
AB  - OBJECTIVES: Thiopurine drugs are the most commonly used steroid-sparing therapies 
      in moderate-to-severe inflammatory bowel disease (IBD). Their complex metabolism 
      and their narrow therapeutic windows means that optimal dosing is difficult. 
      However, weight-based dosing is the norm. Similar antimetabolites are dosed by 
      body composition parameters. In IBD, treatment response and toxicity has been 
      shown to correlate with thiopurine metabolite levels. We sought to determine 
      whether weight or body composition parameters predicted therapeutic 6-thioguanine 
      nucleotide (6TGN) or toxic 6-methylmercaptopurine (6MMP) levels. METHODS: This 
      single-center retrospective cohort study identified 66 IBD patients who had body 
      composition analysis and thiopurine metabolite levels tested. Statistical 
      analysis was performed using Spearman correlation, Kruskal-Wallis, Mann-Whitney, 
      and unpaired t tests and receiver-operator operating characteristic curves. A P 
      value of <0.05 was considered significant. RESULTS: No correlation was identified 
      between 6TGN and any body composition parameters, absolute drug dose or drug 
      dose/kg of fat mass, fat-free mass (FFM), subcutaneous adipose tissue area, or 
      visceral adipose tissue area. However, 6MMP correlated with azathioprine dose, 
      thiopurine dose/kg of body weight, and with several body composition parameters. 
      CONCLUSIONS: No relationship was found between therapeutic metabolite levels and 
      weight or body composition compartments. Higher thiopurine doses, especially in 
      relation to FFM, are associated with higher levels of potentially hepatotoxic 
      6MMP and shunting toward this metabolite. Conventional weight-based dosing to 
      attain therapeutic metabolite levels appears unreliable and may be replaced by 
      metabolite level testing.
FAU - Holt, Darcy Q
AU  - Holt DQ
AD  - Department of Gastroenterology & Hepatology, Monash Health, Clayton, Australia.
AD  - School of Clinical Sciences, Monash University, Clayton, Australia.
FAU - Strauss, Boyd Jg
AU  - Strauss BJ
AD  - School of Clinical Sciences, Monash University, Clayton, Australia.
FAU - Moore, Gregory T
AU  - Moore GT
AD  - Department of Gastroenterology & Hepatology, Monash Health, Clayton, Australia.
AD  - School of Clinical Sciences, Monash University, Clayton, Australia.
LA  - eng
PT  - Journal Article
DEP - 20161027
PL  - United States
TA  - Clin Transl Gastroenterol
JT  - Clinical and translational gastroenterology
JID - 101532142
PMC - PMC5288590
EDAT- 2016/10/28 06:00
MHDA- 2016/10/28 06:01
PMCR- 2016/10/01
CRDT- 2016/10/28 06:00
PHST- 2016/06/14 00:00 [received]
PHST- 2016/08/26 00:00 [revised]
PHST- 2016/09/13 00:00 [accepted]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2016/10/28 06:01 [medline]
PHST- 2016/10/28 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - ctg201656 [pii]
AID - 10.1038/ctg.2016.56 [doi]
PST - epublish
SO  - Clin Transl Gastroenterol. 2016 Oct 27;7(10):e199. doi: 10.1038/ctg.2016.56.