Chemotherapy: irinotecan and UGT1A1: 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: irinotecan and UGT1A1

Sample item

A man with metastatic colorectal cancer develops grade 4 neutropenia and severe delayed diarrhoea after his first dose of irinotecan. Genotyping shows a homozygous reduced-function allele of the enzyme that inactivates its active metabolite SN-38. Which enzyme is it?

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

The answer and the reasoning

C. UDP-glucuronosyltransferase 1A1

Irinotecan is converted by carboxylesterase to SN-38, the active topoisomerase I inhibitor, which UGT1A1 glucuronidates for elimination. The UGT1A1*28 variant reduces this step, so SN-38 accumulates and neutropenia and diarrhoea worsen.

Option by option

  • A. Cytochrome P450 2D6

    CYP2D6 activates tamoxifen and codeine and does not handle SN-38.

  • B. Dihydropyrimidine dehydrogenase

    Dihydropyrimidine dehydrogenase breaks down fluorouracil and capecitabine.

  • C. UDP-glucuronosyltransferase 1A1 (correct)

    Correct. UGT1A1 glucuronidates SN-38, and reduced activity increases toxicity.

  • D. Thiopurine methyltransferase

    Thiopurine methyltransferase inactivates mercaptopurine and azathioprine.

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 C, UDP-glucuronosyltransferase 1A1. Irinotecan is converted by carboxylesterase to SN-38, the active topoisomerase I inhibitor, which UGT1A1 glucuronidates for elimination.

Why is "Cytochrome P450 2D6" not the answer?

CYP2D6 activates tamoxifen and codeine and does not handle SN-38.

Why is "Dihydropyrimidine dehydrogenase" not the answer?

Dihydropyrimidine dehydrogenase breaks down fluorouracil and capecitabine.

Why is "Thiopurine methyltransferase" not the answer?

Thiopurine methyltransferase inactivates mercaptopurine and azathioprine.

What concept does this question test?

It tests Chemotherapy: irinotecan and UGT1A1 in Pharmacology. The UGT1A1*28 variant reduces this step, so SN-38 accumulates and neutropenia and diarrhoea worsen.

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: irinotecan and UGT1A1?

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.