Info

🌱 來自: Adverse Reactions of Irinotecan

Uridine diphosphate glucuronosyltransferase 1A1

• Microsatellite mt results in UGT1A1*28 polymorphism leading to ↓ UGT1A1 expression & activity
• UGT1A1*28 polymorphism typically found in pts w/ Gilbert syndrome; frequency 12-27% in Africans, 5-15% in Caucasians, 1.2-5% in Asians (BJP 2006;62(1):35)
• Important role in the metabolism of etoposide, epirubicin, & most importantly irinotecan
• Irinotecan: Prodrug activated to ethyl-10-hydroxycamptothecin (SN-38) via carboxyl esterase. SN-38 undergoes UGT1A1-catalyzed glucuronidation to form inactive SN-38 glucuronide (SN-38G). Reduced UGT1A1 activity leads to ↑ exposure to SN-38 ↑ tox (diarrhea, myelosuppression) limiting optimal clinical use