Thiopurine metabolites

Chemical Pathology

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 predispose toward hepatotoxicity.

No specific preparation required.
Samples should be collected 4-6 weeks after initiation of treatment or change in dose.

For adults, 4 ml of blood taken into an EDTA tube.

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

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

Samples are referred to an external laboratory for analysis with results expected back within 10 working days.

Ranges and interpretation reported as provided by referral laboratory.

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Page last updated: 19/09/2025 | Page last reviewed: 19/09/2025