ABSTRACT
Figure 12.1 The conversion of the irinotecan to the active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38) is catalyzed by carboxyesterase (CES) 1 and 2. Prolonged levels of SN-38 in the plasma leads to neutropenia. The inactivation of SN-38 to the glucuronide form (SN-38G) is catalyzed by UGT1A1 and UGT1A9. SN-38G is excreted in the bile, where its conversion back to SN38 is catalyzed by enteric bacterial ß-glucuronidase. Increased levels of SN-38 in the intestine can lead to severe diarrhea. Extrahepatic SN-38 is inactivated to SN-38G through a reaction catalyzed by UGT1A1, UGT1A7, and UGT1A9. Cytochrome P-450 (CYP) 3A4 and 3A5 catalyze the conversion of irinotecan to the inactive metabolites 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin (APC) and 7-ethyl-10-[4-amino-1-piperidino] carbonyloxycamptothecin (NPC). Adenosine triphosphate-binding cassette (ABC) B1, C1, C2, and G2 function catalyze the transport of irinotecan out of the liver. Modified from [2,9].
