title: Utility of measuring 6-methylmercaptopurine and 6-thioguanine nucleotide levels in managing inflammatory bowel disease patients treated with 6-mercaptopurine in a clinical practice setting.
abstract: BACKGROUND
  Measuring levels of 6-mercaptopurine (6-MP) metabolites (6-thioguanine nucleotides [6-TGNs] and 6-methylmercaptopurine [6-MMP]) has been proposed as a method to adjust 6-MP dose to optimize therapeutic response while minimizing toxicity in patients with inflammatory bowel disease. A 6-TGN level of >230 pmol/8 x 108 red blood cells (RBCs) has been reported to be associated with a higher efficacy rate, and a level of >450 pmol/8 x 108 RBCs has been reported to be associated with myelotoxicity. A 6-MMP level of >5,700 pmol/8 x 108 RBCs has been reported to be associated with an increased frequency of abnormal results of liver function tests (LFTs).
  
  
  OBJECTIVE
  To report our experience with 6-MMP and 6-TGN levels in a clinical practice setting.
  
  
  METHODS
  Using outpatient clinic medical records, we identified 53 measurements. Indications for measurement, 6-MP dose, and subsequent adjustments were documented.
  
  
  RESULTS
  Indications for measurements included the following: persistent symptoms, 31 cases (58.5%); abnormal LFT results, 7 (13.2%); steroid dependency, 6 (11.3%); anemia, 4 (7.5%); and leukopenia, 2 (3.8%). Of the 31 cases with persistent symptoms, 12 had "therapeutic" 6-TGN levels and other interventions were undertaken. 6-TGN levels were "subtherapeutic" in 19. The 6-MP dose was increased, and remission was achieved in 10 cases after a mean period of 3.6 weeks. Among the cases with abnormal LFT results, 6-MMP levels were high in five and low in two. Among the steroid dependency cases, 6-TGN levels were "subtherapeutic" in five. The dose was increased and steroids were weaned in three cases. The 6-TGN level was high in one of the leukopenia cases and the 6-MP dose was decreased. 6-TGN levels were not above the "target range" in any of the anemia cases.
  
  
  CONCLUSIONS
  Measuring levels of 6-MP metabolites may have a role in customizing 6-MP dosing. This role is not completely clear and needs to be explored in larger well-controlled studies.
authors.affiliation: University of Pittsburgh Medical Center Shadyside, Pennsylvania 15232, USA. mardinih@msx.upmc.edu
authors.forename: Houssam E
authors.initials: HE
authors.lastname: Mardini
authors.forename: George L
authors.initials: GL
authors.lastname: Arnold
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006150:Guanine Nucleotides / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D013873:Thionucleotides / Q000378:metabolism*
chemical_list: D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D015122:Mercaptopurine