What are TGN levels?

A 6-TGN concentration of 235–450 pmol/8 × 108 red blood cells (RBC) was considered the optimal therapeutic range. Poor compliance was defined as a 6-TGN level below 100 pmol/8 × 108 RBC in the absence of a metabolite profile suggesting hypermethylation of thiopurines to MMPN (6-MMPN/6-TGN >11) [20].

Is mercaptopurine toxic?

Symptoms of allergic reaction to mercaptopurine include rash, itching, swelling, dizziness, trouble breathing, and inflammation of the pancreas. In some cases, mercaptopurine may suppress the production of blood cells, both white blood cells and red blood cells. It may be toxic to bone marrow.

What are thiopurine metabolites?

Thiopurine Metabolites – 6-Mercaptopurine (Purinethol) and its imidazolyl derivative, Azathioprine (Imuran), are immunosuppressive drugs. 6-Mercaptopurine (6-MP) is indicated for remission induction and maintenance therapy of acute lymphoblastic leukemia (ALL).

How does allopurinol increase 6-mercaptopurine?

Allopurinol decreases the yield of the pathway of 6-MP to inactive 6-thiouric acid and inhibits first-pass metabolism. This thereby increases the fraction of the drug available for anabolism to the active nucleotide forms 6-TGN and 6-MMPN (16,17).

What is a TGN test?

6-thioguanine nucleotides (6-TGNs) are the active metabolites of the cytotoxic drugs Azathioprine, Mercaptopurine and Thioguanine. Measurement of 6-TGNs helps to confirm therapeutic concentrations and to avoid toxicity.

What is a normal TPMT level?

Reference Range: Normal TPMT activity: 25-65 U/mL – Individuals are predicted to be at low risk of bone marrow toxicity as a consequence of standard thiopurine therapy; no dose adjustment is recommended.

Is it safe to take mercaptopurine?

Mercaptopurine can make you more likely to get infections or may worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.

Can mercaptopurine cause liver damage?

Mercaptopurine can also lead to a distinctive acute, clinically apparent liver injury that usually presents with fatigue and jaundice and a cholestatic or mixed pattern of serum enzyme elevations 1 to 6 months after starting therapy, but sometimes later, particularly following an increase in dose.

What is thiopurine metabolites blood test?

Clinical Information This test is primarily used to verify compliance, optimize therapy, and identify elevated metabolite concentrations that may result in toxicity after initiation of thiopurine drug therapy for the treatment of inflammatory bowel disease.

What does low thiopurine metabolites mean?

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.

How does allopurinol affect mercaptopurine?

Allopurinol inhibits the second step of metabolism, and higher 6-mercaptopurine plasma levels result, with associated toxic effects on the bone marrow and other tissues. The resulting blood dyscrasias, leucopenia, thrombocytopenia or pancytopenia, can be life threatening.

What effect will allopurinol have on the activity of 6-mercaptopurine?

Allopurinol inhibits the enzyme xanthine oxidase (XO), which is one of 3 enzymes responsible for inactivating 6-mercaptopurine (active form of azathioprine). It may also have effects on TPMT activity as one study showed a reduction in methylated metabolites with the combination.