In which situation can TPMT deficiency affect drug metabolism?

TPMT, or thiopurine S-methyltransferase, is an important enzyme involved in the metabolism of certain medications, particularly thiopurines like azathioprine and mercaptopurine. These medications are commonly used in treating conditions such as autoimmune diseases and in preventing organ transplant rejection. Individuals with TPMT deficiency have a reduced ability to metabolize these drugs, leading to an increased risk of toxicity.

When TPMT is deficient, the drugs can accumulate in the body at higher levels than intended, resulting in adverse effects such as bone marrow suppression. Consequently, monitoring TPMT activity in patients who are prescribed azathioprine or mercaptopurine is crucial to prevent complications from overmedication.

In contrast, the other medications listed do not rely on TPMT for their metabolism. Sulfasalazine is metabolized by different pathways, atorvastatin is primarily processed by the liver through cytochrome P450 enzymes, and proton pump inhibitors also follow distinct metabolic routes unrelated to TPMT. Therefore, the interaction and implications of TPMT deficiency are specifically significant in the context of azathioprine or mercaptopurine treatment.