A patient with metastatic colon cancer receiving irinotecan develops severe delayed diarrhea requiring hospitalization. Genotyping reveals reduced activity of the enzyme responsible for glucuronidation of SN-38. Which enzyme is this?
- A CYP3A4
- B Thiopurine methyltransferase
- C UDP-glucuronosyltransferase 1A1 ✓
- D Dihydropyrimidine dehydrogenase
Correct answer: C. UDP-glucuronosyltransferase 1A1
Explanation
Irinotecan is converted by carboxylesterases to its active metabolite SN-38, which is inactivated mainly by UGT1A1-mediated glucuronidation. Patients with UGT1A1*28 reduced-function alleles have higher SN-38 exposure and are at increased risk of severe neutropenia and diarrhea. CYP3A4 handles irinotecan itself, TPMT affects thiopurines, and DPD deficiency predicts fluoropyrimidine toxicity, which kills these distractors.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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