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Thiopurine metabolites

Chemical Pathology

Notes

  • Thiopurine drugs (e.g. azathioprine and mercaptopurine) are catabolised to inactive metabolites by TPMT, which in effect reduces concentrations of the active metabolite, 6-thioguanine nucleotides (6TGN).
  • Measurement of TPMT activity should be performed prior to starting thiopurine drugs. Patients with undetectable activity are generally not treated with thiopurine drugs due to the increased risk of severe side effects including myelosuppression. .
  • In patients who fail to respond to treatment, measurement of levels of thiopurine metabolites, 6-TGN and 6-MMPN may sometimes be useful.
  • Measurement of 6MMPN helps to distinguish patients who are under-dosed or non-compliant (6MMPN levels appropriately low) from those demonstrating resistance to thiopurine drugs, i.e. preferentially metabolising thiopurine drugs to inactive 6MMPN rather than 6TGN (6MMPN disproportionately increased.)
  • In resistant patients, increasing the azathioprine dose is not helpful and further increases 6MMPN levels predisposing toward hepatotoxicity.

Please note that requests are currently only accepted from by consultant gastroenterologists in a limited number of patients who are clinically difficult to treat.

Sample requirements

Samples should be collected at 4 weeks from start of treatment or after any change in dose.

For adults, 4 ml of blood taken into an EDTA tube a Full Blood Count should also be requested.

EDTA with cap

Storage/transport

Send at ambient temperature to the laboratory. If unavoidable samples can be refrigerated overnight.

Required information

Relevant clinical details including reason for the request and current thiopurine drug regimes.

Turnaround times

Samples are sent for analysis to Guy's and St Thomas' Hospital, London with results expected back within 2 weeks.

Reference ranges and Result Interpretation

235-450 pmol 6-TGN/8x10^8 cells: Maximum drug efficacy.

Increased risk of hepatotoxicity when 6-MMPN is >5700 pmol 6MMPN/8x10^8 cells.

Further information

Lab Tests Online

González-Lama Y, Gisbert JP Monitoring thiopurine metabolites in inflammatory bowel disease Frontline Gastroenterology 2016;7:301-307

Page last updated: 29/12/2023

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