Mercaptopurine metabolite results in clinical gastroenterology practice

Aliment Pharmacol Ther. 2003 Jan;17(1):69-73. doi: 10.1046/j.1365-2036.2003.01392.x.

Abstract

Background: Azathioprine (AZA) and its active metabolite mercaptopurine (MP) are frequently used in the management of inflammatory bowel disease. Measurement of the AZA/MP metabolites, thioguanine (TG) and methylmercaptopurine (MMP), has been suggested as a means to optimize therapy with AZA/MP in inflammatory bowel disease.

Aim: To evaluate the results of initial AZA/MP metabolite panels sent by gastroenterologists during the first year of its widespread availability.

Methods: Initial AZA/MP metabolite panels sent by gastroenterologists to a single laboratory were reviewed and the metabolite panels were interpreted.

Results: Initial metabolite levels were reviewed for 9187 patients. Noncompliance was detected in 263 patients (3%) and under-dosing in 4260 patients (46%). 534 patients (6%) had levels that were consistent with preferential metabolism via the TPMT pathway. The therapeutic goal was achieved in 2444 patients (27%) and an additional 552 patients (6%) had appropriate TG levels but potential hepatotoxicity. 936 patients (10%) had potential TPMT deficiency, and 58 patients (1%) had potential TPMT absence and were at risk for leukopenia. 140 patients (2%) had too high a dose.

Conclusions: Measurement of AZA/MP metabolites can be used by practising gastroenterologists to identify potential reasons for nonresponse to AZA or MP, and to identify patients at risk for certain drug-related toxicities.

MeSH terms

  • Azathioprine / metabolism*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / metabolism
  • Mercaptopurine / analogs & derivatives*
  • Mercaptopurine / metabolism
  • Mercaptopurine / therapeutic use*
  • Patient Compliance
  • Risk Factors
  • Thioguanine / metabolism*

Substances

  • 6-methylthiopurine
  • Mercaptopurine
  • Thioguanine
  • Azathioprine