The utility of 6-thioguanine metabolite levels in managing patients with inflammatory bowel disease.

Abstract

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 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.

• Authors: Benjamin A Goldenberg, Patricia Rawsthorne, Charles N Bernstein
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 99 Issue 9 Pg. 1744-8 (Sep 2004) ISSN: 0002-9270 [Print] United States
• PMID: 15330913 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Biomarkers
• 6-methylthiopurine
• Mercaptopurine
• Thioguanine
• Azathioprine

Topics

• Adult
• Azathioprine (administration & dosage, pharmacokinetics)
• Biomarkers (blood)
• Cohort Studies
• Colitis, Ulcerative (blood, diagnosis, drug therapy)
• Crohn Disease (blood, diagnosis, drug therapy)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Inflammatory Bowel Diseases (blood, diagnosis, drug therapy)
• Male
• Maximum Tolerated Dose
• Mercaptopurine (administration & dosage, analogs & derivatives, pharmacokinetics)
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Prospective Studies
• Risk Assessment
• Severity of Illness Index
• Thioguanine (blood)
• Treatment Outcome