What does a high TPMT level mean?
High TPMT activity: > 65 U/mL – Individuals are not predicted to be at low risk for bone marrow toxicity as a consequence of standard thiopurine dosing, but may be at risk for therapeutic failure due to excessive inactivation of thiopurine drugs.
What does TPMT stand for in a blood test?
Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body’s immune system.
What is TPMT deficiency?
Which drugs are thiopurines?
MN There are 3 types of thiopurines that have been used for inflammatory bowel disease (IBD) therapy: azathioprine, 6-mercaptopurine, and thioguanine. The first 2 are approved for the treatment of IBD, and the third has been tested in clinical trials.
How are thiopurines metabolized?
Thiopurine metabolism The metabolism of MP involves three competing pathways: the first being degradation to TUA which is then excreted, the second is through methylation by TPMT into MeMP, and the third is the breakdown of MP into TIMP catalysed by HPRT. TIMP is then further metabolised via IMPDH into TGMP.
What are thiopurines used for?
Thiopurine drug therapy is used for autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent rejection after solid organ transplant. The inactivation of thiopurine drugs is catalyzed in part by thiopurine methyltrasferase (TPMT) and nudix hydrolase 15 (NUDT15).
Where is the TPMT gene located?
Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. A pseudogene for this locus is located on chromosome 18q. Chr.
What is thiopurine methyltransferase?
What is being tested? Thiopurine methyltransferase (TPMT) is an enzyme that breaks down (metabolizes) a class of drugs called thiopurines. These drugs are used to suppress the immune system and are prescribed to treat various immune-related conditions or blood disorders (e.g., leukemia).
How do you test for thiopurine toxicity?
Phenotype test for TPMT If someone has little to no detectable TPMT activity, that person is at risk of developing severe side effects to thiopurine drugs. Usually the healthcare practitioner will find an alternative drug treatment. Low to intermediate TPMT activity also puts individuals at increased risk for toxicity.
Which genotyping should be performed prior to thiopurine treatment?
The U.S. Food and Drug Administration (FDA) and prescribing information for azathioprine and mercaptopurine recommend either TPMT genotyping or phenotyping prior to thiopurine treatment.
Are You at risk for thiopurine drug toxicity?
Individuals in both categories are at an increased risk for thiopurine drug toxicity, which can affect the activity of the bone marrow (myelosuppression) and lead to very reduced levels of blood cells, such as red blood cells, white blood cells and platelets (hematopoetic toxicity).