Figure 1

A PBPK model to analyze pharmacokinetic properties of irinotecan and metabolites. We constructed a PBPK model to simulate time profiles of the accumulations of irinotecan and the metabolites. We included compartments for rapid and late equilibrium, liver, small and large intestine, biliary transits, urine, feces, and biliary T-tubes.The ordinary differential equations of this model are described in the Additional file 1. CL₁₂, clearance from a rapid to a late equilibrium compartments; CL_CES,1, metabolic clearance of irinotecan by CES2 to form SN-38; CL_CES,2, metabolic clearance of NPC by CES2 to form SN-38; CL_bile, biliary clearance to a transit compartment; CL_bile,T, biliary clearance to biliary T-tube; CL_3A4,1, metabolic clearance of irinotecan by CYP3A4 to form APC; CL_3A4,2, metabolic clearance of irinotecan by CYP3A4 to form NPC; CL_R, renal clearance; CL_UGT, metabolic clearance of SN-38 by UGT to form SN-38G; CPT-11, irinotecan; k₂₁, kinetic constant from a late to a rapid equilibrium compartment; k_a, absorption rate constant; k_feces, kinetic constant for the transit from large intestine to feces; k_LI, kinetic constants for the transit from small intestine to large intestine; K_P,H, concentration ratio between liver and rapid equilibrium compartment; k_transit, kinetic constant for the transit in bile compartments to small intestine; Q_H, blood flow rate in liver.