Chemotherapy: methotrexate interaction mechanism: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Chemotherapy: methotrexate interaction mechanism

Sample item

A boy with osteosarcoma receiving high-dose methotrexate is given ibuprofen and piperacillin for fever. He develops severe mucositis and pancytopenia with a persistently high methotrexate level. What best explains the toxicity?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. Competition for tubular secretion delays methotrexate clearance

Methotrexate is eliminated mainly by renal excretion, including active tubular secretion. Weak organic acids such as NSAIDs, penicillins and probenecid compete for this transport, and NSAIDs can also lower renal blood flow, so the level stays high and toxicity follows.

Option by option

  • A. Induction of dihydrofolate reductase in marrow cells

    Induction of dihydrofolate reductase would reduce rather than increase methotrexate toxicity.

  • B. Reduced intestinal absorption of folinic acid

    Folinic acid is given parenterally for rescue, and its absorption is not the issue.

  • C. Inhibition of hepatic CYP3A4 metabolism of methotrexate

    Methotrexate is not significantly metabolised by CYP3A4 in the liver.

  • D. Competition for tubular secretion delays methotrexate clearance (correct)

    Correct. NSAIDs and penicillins compete with methotrexate for tubular secretion.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, Competition for tubular secretion delays methotrexate clearance. Methotrexate is eliminated mainly by renal excretion, including active tubular secretion.

Why is "Induction of dihydrofolate reductase in marrow cells" not the answer?

Induction of dihydrofolate reductase would reduce rather than increase methotrexate toxicity.

Why is "Reduced intestinal absorption of folinic acid" not the answer?

Folinic acid is given parenterally for rescue, and its absorption is not the issue.

Why is "Inhibition of hepatic CYP3A4 metabolism of methotrexate" not the answer?

Methotrexate is not significantly metabolised by CYP3A4 in the liver.

What concept does this question test?

It tests Chemotherapy: methotrexate interaction mechanism in Pharmacology. Weak organic acids such as NSAIDs, penicillins and probenecid compete for this transport, and NSAIDs can also lower renal blood flow, so the level stays high and toxicity follows.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Chemotherapy: methotrexate interaction mechanism?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.