6-mercaptopurine metabolite levels in children with inflammatory bowel disease.
OBJECTIVE
Some authors suggest that efficacy of 6-mercaptopurine (6-MP) in patients with inflammatory bowel disease correlates with circulating 6-thioguanine (6-TG) levels more than 235 pmol/8 x 10(8) red blood cells. The authors evaluated the relation between 6-MP metabolite levels and disease activity in children and adolescents with inflammatory bowel disease.


METHODS
Clinical status and hematologic and hepatic parameters were determined in 101 children with inflammatory bowel disease from a single center and compared with 6-MP metabolite levels.


RESULTS
There was a trend for higher 6-TG levels among patients in remission than among those with active disease (217 vs. 173); however the difference was not statistically significant ( P = 0.09). The likelihood of therapeutic response did not increase significantly at 6-TG levels greater than 235 pmol/8 x 10(8) red blood cells (odds ratio 1.7; P = 0.1). In the current study, 58% of patients in remission had 6-TG levels less than 235. However, serial measurements of 6-MP metabolite levels in 50 patients with active disease showed that increasing 6-TG levels correlated significantly with disease remission in patients followed up longitudinally ( P = 0.04). Leukopenia was significantly associated with high 6-TG levels ( P = 0.03) but not with clinical response ( P = 0.2).


CONCLUSIONS
These data suggest that the target range of 6-TG levels previously described by others did not apply to 58% of the pediatric patients with IBD in remission. However, serial monitoring of 6-MP metabolite levels in individual patients with active disease should allow dose escalation and induction of remission while minimizing the risk of toxicity.
Gupta
P
P
Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The University of Chicago Children's Hospital, Chicago, Illinois 60637, USA. pgupta@peds.bsd.uchicago.edu
Gokhale
R
R
Kirschner
B S
BS
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D001379:Azathioprine / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D002648:Child; D003430:Cross-Sectional Studies; D004912:Erythrocytes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D016017:Odds Ratio; D012189:Retrospective Studies; D013866:Thioguanine / Q000097:blood / Q000378:metabolism*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine