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. Author manuscript; available in PMC: 2022 Jan 28.
Published in final edited form as: Pharmacotherapy. 2020 Oct 19;40(11):1108–1129. doi: 10.1002/phar.2463

Figure 2. Irinotecan metabolism.

Figure 2.

Irinotecan is a prodrug that undergoes conversion to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), via carboxylesterase (CES)-mediated hydrolysis. CYP3A4/CYP3A5 oxidize SN-38 into inactive APC and NPC. SN-38 targets topoisomerase I to cause apoptosis. Detoxification occurs via uridine diphosphate-glucuronosyltransferase isoform 1A1 (UGT1A1). As the resulting glucuronide, SN-38G, is primarily excreted into bile, bacterial beta-glucuronidases can re-activate the metabolite. CES = carboxylesterases; NPC = 7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin; APC = 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin; ABCB1, ABCC2, ABCG2 = ABC dATP-binding cassette transporters; SN-38 = 7-ethyl-10-hydroxycamptothecin; SN-38G = glucuronidated SN-38; TOP1 = DNA Topoisomerase I; UGT1A1 = uridine-diphosphoglucuronate glucuronosyltransferase 1A1 (encoded by UGT1A1).