PMID- 29522107
OWN - NLM
STAT- MEDLINE
DCOM- 20190523
LR  - 20190523
IS  - 1536-4844 (Electronic)
IS  - 1078-0998 (Linking)
VI  - 24
IP  - 4
DP  - 2018 Mar 19
TI  - Late-onset Rise of 6-MMP Metabolites in IBD Patients on Azathioprine or 
      Mercaptopurine.
PG  - 892-896
LID - 10.1093/ibd/izx081 [doi]
AB  - BACKGROUND: The thiopurines azathioprine and mercaptopurine remain pivotal 
      maintenance treatments in inflammatory bowel disease (IBD); however, up to 
      15%-20% of patients preferentially produce the hepatotoxic metabolite 
      6-methylmercaptopurine (6MMP) at the expense of the therapeutic 6-thioguanine 
      nucleotides (6TGN). This metabolic shunting usually begins within 3 months of 
      therapy. We noted patients developing shunting many months or years after 
      starting treatment and aimed to determine how often this late shunting occurs and 
      whether this could be explained by patient factors or concomitant medications. 
      METHODS: The New Zealand database of thiopurine metabolite results from 2002 to 
      2016 (19085 6TGN/6MMP pairs from 7130 patients) was interrogated to identify 
      patients developing a 6MMP/6TGN ratio >20 after at least 4 months treatment. 
      Dosing history, concomitant therapy, and comorbidity data were assessed. RESULTS: 
      Fifteen percent of database patients developed preferential 6-MMP production, and 
      of these, 29 patients had late-onset shunting with sufficient data available for 
      validation. This extrapolates to 90 patients in total, representing 1.7% of IBD 
      patients on thiopurines, or 10% of all those with preferential 6-MMP production. 
      Time from starting therapy to shunting was 5 months to 10.4 years (median, 21 
      months). Eleven patients had abnormal liver function when shunting was 
      recognized, all with 6MMP >5900 pmol/8 x 108 red blood cells. No common factors 
      were found to explain the late onset. CONCLUSIONS: Some IBD patients develop 
      preferential 6MMP production many months or years after commencing therapy. This 
      is important when considering frequency of metabolite monitoring, failure of 
      therapy, or abnormal liver function. 
      10.1093/ibd/izx081_video1izx081.video15746667546001.
FAU - Munnig-Schmidt, Erik
AU  - Munnig-Schmidt E
AD  - Department of Gastroenterology, VU Medical Centre, Amsterdam, the Netherlands.
FAU - Zhang, Mei
AU  - Zhang M
AD  - Department of Medicine, University of Otago Christchurch, Christchurch, New 
      Zealand.
FAU - Mulder, Chris J
AU  - Mulder CJ
AD  - Department of Gastroenterology, VU Medical Centre, Amsterdam, the Netherlands.
FAU - Barclay, Murray L
AU  - Barclay ML
AD  - Department of Medicine, University of Otago Christchurch, Christchurch, New 
      Zealand.
AD  - Departments of Gastroenterology and Clinical Pharmacology, Christchurch Hospital, 
      Christchurch, New Zealand.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Azathioprine/*therapeutic use
MH  - Female
MH  - Humans
MH  - Inflammatory Bowel Diseases/drug therapy/*metabolism
MH  - Male
MH  - Mercaptopurine/*analogs & derivatives/metabolism/*therapeutic use
MH  - Middle Aged
MH  - New Zealand
MH  - Thioguanine/*metabolism
MH  - Young Adult
EDAT- 2018/03/10 06:00
MHDA- 2019/05/24 06:00
CRDT- 2018/03/10 06:00
PHST- 2018/03/10 06:00 [pubmed]
PHST- 2019/05/24 06:00 [medline]
PHST- 2018/03/10 06:00 [entrez]
AID - 4924361 [pii]
AID - 10.1093/ibd/izx081 [doi]
PST - ppublish
SO  - Inflamm Bowel Dis. 2018 Mar 19;24(4):892-896. doi: 10.1093/ibd/izx081.