Div. of Pediatric Gastroenterology, Dep. of Gastroenterology, & Dep. of Clinical Pharmacology, Sheba Medical Center, Tel-Hashomer.

Background: 6-mercaptopurine (6-MP) and azathioprine (AZA) are effective and widely used in treating inflammatory bowel disease. The effects of 6-MP are mediated via its intracellular conversion to 6-thioguanine (6- TG) and 6-methylmercaptopurine (6-MMP) nucleotide metabolites. Some authors suggest that efficacy of 6-MP in patients with IBD correlates with 6-TG levels more than 235 pmol/8×108 RBC. However, other studies have not demonstrated a consistent correlation between clinical response and 6-TG levels. Drug-relatd toxicity has also been attributed to high metabolite levels. Aim: The purpose of this study was to evaluate the correlation between 6-MP metabolite levels to therapeutic response and drug-induced toxicity in patients with IBD. Methods: Therapeutic response was determined in 30 patients with IBD (27 CD, 3 UC) coincidentally with hematologic, hepatic and pancreatic laboratory parameters, and correlated with erythrocyte metabolite levels. Results: A trend towards correlation was found between 6-TG levels above 235 pmol/8x108RBC and remission (p=0.06). No correlation was found between 6-MP dose and 6-TG levels (r = 0.22), and between 6-MP levels and disease activity (r = 0.16). Leukopenia, observed in 3 patients, did not correlate with 6-TG level or 6-MP dose. Conclusions: Measurement of 6-TG metabolites may be helpful in determining the adequacy of 6-MP/AZA dosage, and may be used to optimise the dose and achieve metabolite levels which correlate with remission. A larger scale study is needed to assess correlation of metabolite levels with drug toxicity.

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