The utility of 6-thioguanine metabolite levels in managing patients with inflammatory bowel disease.
OBJECTIVE
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 x 10(8) red blood cells, RBC) correlated with clinical remission or leukopenia, and if 6-MMP level was a marker for hepatotoxicity (>5,700 pmol/8 x 10(8) 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 x 10(8) 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 remission versus those with active disease (mean 325 +/- 284 vs 223 +/- 159 pmol/8 x 10(8) RBC, p= 0.2). No hepatotoxicity was observed, although 12.2% had 6-MMP levels > 5,700 pmol/8 x 10(8) 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 levels versus 6-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.
University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, 804F-715 McDermot Avenue, Winnipeg, Manitoba, Canada R3E 3P4.
Benjamin A
BA
Goldenberg
Patricia
P
Rawsthorne
Charles N
CN
Bernstein
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D020714:Maximum Tolerated Dose; D015122:Mercaptopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013866:Thioguanine / Q000097:blood*; D016896:Treatment Outcome
D015415:Biomarkers; C010240:6-methylthiopurine; D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine