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Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition; Orlando, October 22-24, 1998

6-MP METABOLITE LEVELS PREDICT CLINICAL EFFICACY AND DRUG TOXICITY IN PEDIATRIC IBD

Dubinsky, M; Lamothe, S*; Sinnett, D*; Théorét, Y*; Seidman, E

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Journal of Pediatric Gastroenterology & Nutrition: October 1998 - Volume 27 - Issue 4 - p 465
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Abstract 9

BACKGROUND: The immunosuppressive properties of 6-MP are mediated via the intracellular transformation of 6-MP to its active metabolites (6-TG, 6-MMP nucleotides). Our preliminary study (Gut 1996; 39: 401-406) suggested that measurement of 6-MP metabolite levels predict clinical efficacy and tolerance to azathioprine or 6-MP. AIM: To evaluate the measurement of 6-MP metabolite levels (6-TG, 6-MMP) in relation to clinical disease activity and drug toxicity. METHODS: Blood was sampled (n=92) prior to daily administration of 6-MP in 55 IBD patients (CD n=51, UC n=4) receiving 1-1.5 mg/kg/day (≥ 4 mo). Erythrocyte free bases 6-TG and 6-MMP were measured (pmol/8×108 RBC) using reverse phase HPLC. Hepatic, pancreatic and hematological tests were obtained every 3 mo. Clinical remission was defined as a Harvey Bradshaw Index < 5 in those patients off corticosteroids or weaned to prednisone ≤ 0.4 mg/kg/od. Treatment failures were defined as non-responders (HBI > 5 or steroid dependence), or cessation of 6-MP due to side effects. (Table)

TABLE
TABLE

CONCLUSIONS: A 6-TG level of > 225 was associated with remission. Excessive 6-TG and 6-MMP levels were associated with leukopenia and hepatotoxicity, respectively. Negligible metabolite levels detected non-compliance as a cause of treatment failure in 2/31 cases. 6-MP metabolite levels thus predict both clinical responsiveness and drug-related toxicity. Supported by the FRSQ and Fondation Charles-Bruneau.

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PLENARY SESSION II

© 1998 Lippincott Williams & Wilkins, Inc.