Synonyms

6-Thioguanine Nucleotides (6TGN)
6-Methylmercaptopurine Nucleotides (6MMPN)

Clinical Indications

The immunosuppressive effect of thiopurine drugs is mediated primarily by the cytotoxic metabolite, 6TGN, and incorporation of these false bases into DNA. Accumulation of high levels of 6TGN is also responsible for some side effects of thiopurine drugs, and has been associated with leucopenia. Furthermore, high levels of the inactive metabolite 6MMPN, which is formed via the TPMT pathway, may be associated with hepatotoxicity.

Indications for measuring thiopurine metabolites include suspected non-compliance or treatment with a suboptimal dose or failure to respond to standard doses of thiopurine drugs. 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 to hepatotoxicity.

Request Form

Combined Pathology Blood form (Yellow/Black)

Availability

Referral test: Analysed by Biochemistry, Birmingham City Hospital, if specific criteria met.

Specific Criteria

Requests will not be undertaken unless agreed with the Consultant Biochemist.

Patient Preparation

Sample should be taken 4 weeks from the start of treatment or a change in dose.

Turnaround Time

2 weeks

Specimen

Whole blood (EDTA)

Volume

1ml

Container

Pink/purple top (EDTA) tube

For paediatrics a red top (EDTA) tube is required.

Causes for Rejection

Unlabelled sample. Not meeting specific criteria for analysis.

Reference Range

235 – 450 pmol 6TGN/8x108 cells
Maximum drug efficacy in inflammatory bowel disease.

>5700 pmol 6MMPN/8x108 cells
Associated with increased risk of hepatotoxicity.

Lab. Handling

Processing: Do not centrifuge or separate. Store at 4°C as whole blood in the  separating fridge (CB39), referral rack.

Referral: TGN and send or BPRO and save sample.