Figure 3.

Schematic model depicting known and new insight into the metabolism and transport of CPT-11, SN-38, and SN-38G and the proposed effect on treatment-related toxicities and response. Increased SN-38 exposure due to combined SLCO1B1 and UGT1A1 variants correlates with an increased risk for neutropenia. Increased intestinal SN-38G, due to reduced ABCC5 hepatic efflux, may lead to increased risk for diarrhoea as SN-38G is converted to SN-38 via intestinal β-glucoronidases. Circles with check marks indicate an effect on neutropenia (N), diarrhea (D), and progression-free survival (P).