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Paediatric Laboratory Medicine

Azathioprine Metabolites (6-TG, 6-MMP)

Clinical Significance

Azathioprine, which is a pro drug of 6-mercaptopurine (6-MP), is considered an effective immunosuppressive treatment of inflammatory bowel disease, particularly in patients with steroid resistant disease. However, the use of azathioprine is limited by both its long onset of action (three to four months) and drug toxicities, which include hepatotoxicity, bone marrow suppression, pancreatitis, and allergic reactions. Long term drug use has been associated with neoplasia. 

Azathioprine is converted to 6-mercaptopurine in vivo, where it is subsequently metabolized into two active metabolites; either 6-thioguanine nucleotides (6-TG) by the enzyme IMPDH, or to 6-methyl-mercaptopurine ribonucleotides (6-MMRP) by the enzyme thiopurine methyltransferase TPMT. 6-TG is considered cytotoxic and thus, is associated with bone marrow suppression, while 6-MMRP is associated with hepatotoxicity. In population studies, the activity of the enzyme TPMT has been shown to be trimodal with 90 per cent of subjects having high activity, 10 per cent intermediate activity, and 0.3 per cent with low or no activity. This variation in TPMT activity has been related to three distinct TPMT mutations and has permitted the development of TPMT genotyping based on a polymerase chain reaction (PCR). Genetic analysis has been explored as a technique to proactively identify patients at risk for bone marrow suppression. Those with high TPMT activity may be started at a higher initial dose of therapy, while those with low TPMT activity may not be good candidates for azathioprine therapy.

Test Name

Azathioprine Metabolites (6-TG, 6-MMP)

Alternate Name/ Synonym

Imuran

Test Code

THIOL

Drug Class

Immunosuppressive

Division

Therapeutic Drug Monitoring - TDM

Method

HPLC

External Proficiency Testing

NA

Turn Around Time

10 - 14 days

Disease/Condition

Immunosuppressive

Specimen Type

Whole Blood (EDTA) - Do not Separate

Minimum Specimen Requirements

5.0 mL

Optimal Collection Time

Trough: 0 - 30 minutes prior to dose

Storage/Transportation

4° C (transport with a cool pack if possible)

Approval is not required

CPT Codes

82491

Shipping and Contact Information

The Hospital for Sick Children
Rapid Response Laboratory
170 Elizabeth Street, Room 3642
Toronto, ON
M5G 2G3
Canada
Phone: 416-813-7200
Phone: 1-855-381-3212

Therapeutic Range

6-TG: 400 – 750 pmol/8 x 106 RBC
6-MMP: < 6600 pmol/8 x 106 RBC

Critical Values

6-MMP: > 6600 pmol/8 x 106 RBC