PMID- 21122558
OWN - NLM
STAT- MEDLINE
DCOM- 20110411
LR  - 20220310
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Linking)
VI  - 4
IP  - 5
DP  - 2010 Nov
TI  - A prospective evaluation of the impact of allopurinol in pediatric and adult IBD 
      patients with preferential metabolism of 6-mercaptopurine to 
      6-methylmercaptopurine.
PG  - 546-52
LID - 10.1016/j.crohns.2010.03.004 [doi]
AB  - BACKGROUND: 6-mercaptopurine (6-MP) is used for the induction and maintenance of 
      remission of inflammatory bowel disease (IBD). 6-MP is converted into 
      6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) 
      intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. 
      This study prospectively evaluated the effect of allopurinol on 6-MP metabolites 
      in adult and pediatric IBD patients. Additionally, we quantified the prevalence 
      of preferential metabolism towards 6-MMP through a retrospective analysis of IBD 
      patients. METHODS: Twenty patients (10 adult; 10 pediatric) with evidence of 
      preferential metabolism towards 6-MMP, (6-TGN<250 pmol/8x10(8) RBCs and 6-MMP>5000 
      pmol/8x10(8) RBCs) were prospectively treated with allopurinol 100 mg daily and up 
      to 100 mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement. 
      RESULTS: The median dose of 6-MP for adults decreased from 100mg daily (range: 
      37.5-150 mg) to 25mg daily (range: 12.5-50 mg). The median dose of 6-MP for 
      pediatric patients decreased from 50 mg (range: 25-50 mg) to 10.7 mg (range: 10.7 
      to 21.4 mg). Mean 6-TGN levels in all subjects increased from 197.4 (+/- 59) to 
      284.8 (+/- 107) pmol/8x10(8) RBCs (p=0.0005). Mean 6-MMP levels in all subjects 
      decreased from a mean of 7719.8 (+/- 4716) to 404.8 (+/- 332) pmol/8x10(8) RBCs 
      (p=0.0004). There were no complications associated with allopurinol therapy. 
      Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism 
      towards 6-MMP. The proportion of preferential metabolism was equal in adults and 
      pediatric patients. CONCLUSION: Our results indicate that the addition of 
      allopurinol safely shifts metabolite production in both adult and pediatric IBD 
      patients and that there is a high prevalence of preferential metabolism towards 
      6-MMP among IBD patients.
CI  - Published by Elsevier B.V.
FAU - Gerich, Mark E
AU  - Gerich ME
AD  - Department of Internal Medicine, Division of Gastroenterology, University of 
      California Davis Health System, Sacramento, CA 95817, United States.
FAU - Quiros, J Antonio
AU  - Quiros JA
FAU - Marcin, James P
AU  - Marcin JP
FAU - Tennyson, Linda
AU  - Tennyson L
FAU - Henthorn, Maria
AU  - Henthorn M
FAU - Prindiville, Thomas P
AU  - Prindiville TP
LA  - eng
PT  - Journal Article
DEP - 20100526
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - 6V404DV25O (6-methylthiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.67 (thiopurine methyltransferase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Allopurinol/administration & dosage/pharmacology/*therapeutic use
MH  - Child
MH  - Child, Preschool
MH  - Drug Administration Schedule
MH  - Enzyme Inhibitors/administration & dosage/pharmacology/*therapeutic use
MH  - Female
MH  - Guanine Nucleotides/blood
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/*metabolism/*therapeutic use
MH  - Inflammatory Bowel Diseases/*drug therapy/enzymology/*metabolism
MH  - Male
MH  - Mercaptopurine/administration & dosage/analogs & 
      derivatives/blood/*metabolism/*therapeutic use
MH  - Methyltransferases/genetics/metabolism
MH  - Middle Aged
MH  - Phenotype
MH  - Prevalence
MH  - Prospective Studies
MH  - Thionucleotides/blood
MH  - Young Adult
EDAT- 2010/12/03 06:00
MHDA- 2011/04/13 06:00
CRDT- 2010/12/03 06:00
PHST- 2009/11/16 00:00 [received]
PHST- 2010/03/12 00:00 [revised]
PHST- 2010/03/13 00:00 [accepted]
PHST- 2010/12/03 06:00 [entrez]
PHST- 2010/12/03 06:00 [pubmed]
PHST- 2011/04/13 06:00 [medline]
AID - S1873-9946(10)00050-4 [pii]
AID - 10.1016/j.crohns.2010.03.004 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2010 Nov;4(5):546-52. doi: 10.1016/j.crohns.2010.03.004. Epub 
      2010 May 26.