title: Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine.
abstract: BACKGROUND
  Many non-responders to azathioprine or mercaptopurine (6-mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6-methylmercaptopurine instead of the active 6-tioguanine (6-tioguanine) metabolites.
  
  
  OBJECTIVE
  To describe the use of allopurinol in mercaptopurine/azathioprine non-responders to deliberately shunt metabolism of mercaptopurine towards 6-tioguanine.
  
  
  METHODS
  Fifteen thiopurine non-responders whose metabolites demonstrated preferential metabolism towards 6-methylmercaptopurine are described. Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to 25-50% of the original dose. Patients were followed clinically and with serial 6-tioguanine and 6-methylmercaptopurine metabolite measurements.
  
  
  RESULTS
  After initiating allopurinol, 6-tioguanine levels increased from a mean of 185.73 +/- 17.7 to 385.4 +/- 41.5 pmol/8 x 10(8) red blood cells (P < 0.001), while 6-methylmercaptopurine decreased from a mean of 10 380 +/- 1245 to 1732 +/- 502 pmol/8 x 10(8) RBCs (P < 0.001). Allopurinol led to a decrease in white blood cell from a mean of 8.28 +/- 0.95 to 6.1 +/- 0.82 x 10(8)/L (P = 0.01).
  
  
  CONCLUSIONS
  The addition of allopurinol to thiopurine non-responders with preferential shunting to 6-methylmercaptopurine metabolites appears to be an effective means to shift metabolism towards 6-tioguanine.
authors.affiliation: Section of Gastroenterology, University of Chicago Medical Center, Chicago, IL 60637, USA. msparrow@medicine.bsd.uchicago.edu
authors.forename: M P
authors.initials: MP
authors.lastname: Sparrow
authors.forename: S A
authors.initials: SA
authors.lastname: Hande
authors.forename: S
authors.initials: S
authors.lastname: Friedman
authors.forename: W C
authors.initials: WC
authors.lastname: Lim
authors.forename: S I
authors.initials: SI
authors.lastname: Reddy
authors.forename: D
authors.initials: D
authors.lastname: Cao
authors.forename: S B
authors.initials: SB
authors.lastname: Hanauer
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D000963:Antimetabolites / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D015122:Mercaptopurine / Q000627:therapeutic use*; D013866:Thioguanine / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D000493:Allopurinol; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine