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Thiopurine Metabolites

Therapy with thiopurine immunosuppressive drugs

Sample: EDTA whole blood (Refrigerate 4^oC, see instructions)

Status: UK Lab

Includes: TPMT (Thiopurine Methyltransferase), 6-TGN (6-Thioguanine nucleotides), 6-MMPN (6-Methylmercaptopurine nucleotides)

Schedule: One week

Remarks: The immunosuppressive effect of thiopurine drugs  (Azathioprine) is mediated primarily by the formation of cytotoxic thioguanine nucleotides (6-TGN) and the incorporation of these false bases to the DNA. Accumulation of 6-TGN also is associated with leucopaenia. High levels of the inactive 6-MMPN (formed via the TPMT pathway) are associated with hepatotoxicity.

Patients with low or deficient TMPT activity shunt 6-MMPN towards to increased 6-TGN production. It is therefore strongly advised that patients TMPT status to be tested prior starting thiopurine therapy.  

Testing for 6-MMPN helps to ditinguish under-dosed patients (6-MMPN correctly low) from those patinets demostrating resistance to thiopurine drugs (i.e. those that prefferentially metabolise thiopurine durgs to iancative 6-MMPN rather than 6-TGN).