The Utility of 6-Thioguanine Metabolite Levels in Managing Patients with Inflammatory Bowel Disease

Goldenberg, Benjamin A.; Rawsthorne, Patricia; Bernstein, Charles N.
September 2004
American Journal of Gastroenterology;Sep2004, Vol. 99 Issue 9, p1744
Academic Journal
OBJECTIVES: We aimed at determining the utility of measuring 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in inflammatory bowel disease (IBD) patients on azathioprine (AZA) or 6-mercaptopurine (6-MP), whether the described therapeutic range for 6-TG (235–400 pmol/8× 108 red blood cells, RBC) correlated with clinical remission or leukopenia, and if 6-MMP level was a marker for hepatotoxicity (>5,700 pmol/8× 108 RBC).METHODS: Study eligibility included an IBD diagnosis of>6 months and either active disease or disease remission of<6 months and the use of AZA/6-MP for>10 wk consecutively. Metabolite levels were evaluated against clinical status, CBC, and hepatic parameters.RESULTS: Seventy-four of 166 AZA/6-MP users were eligible. 6-TG levels>235 pmol/8× 108 RBC were found in 22/59 (38%) with active disease and in 7/15 with remission (47%,p= 0.16). There was a trend of higher 6-TG levels among those in remissionversusthose with active disease (mean 325± 284vs223± 159 pmol/8× 108 RBC,p= 0.2). No hepatotoxicity was observed, although 12.2% had 6-MMP levels>5,700 pmol/8× 108 RBC. The correlation between 6-MP dose and 6-TG levels was weak (r= 0.22,p= 0.08). The 6-TG level did not correlate with WBC. There were five instances, each of markedly low levels of both 6-TG and 6-MMP, suggesting noncompliance and of marked 6-MMP levelsversus6-TG.CONCLUSIONS: There was a poor correlation between 6-TG levels and remission. Nonetheless, the measurements of these levels are helpful when patients are on high doses but not achieving remission since noncompliance or metabolism favoring 6-MMP can be established.


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