Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: a review of four cases and the literature.
BACKGROUND
At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN).


METHODS
A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment.


RESULTS
All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8 x 10(8) red blood cells. Two patients experienced reversible leukopenia.


CONCLUSIONS
Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised.
Witte
T N
TN
Department of Internal Medicine, The George Washington University, Washington, DC 20037, USA.
Ginsberg
A L
AL
D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000963:Antimetabolites / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001711:Biotransformation; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged
D000963:Antimetabolites; D007166:Immunosuppressive Agents; D000493:Allopurinol; D015122:Mercaptopurine