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Table 3 Kinetic parameters for the protein binding, tissue distribution, and urinary and biliary excretion of ketoconazole, irinotecan, and their metabolites.

From: Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation

Compound f B Kp GI Kp Liver Kp Adipose Kp NET CLU,R[mL/min/kg] CLU,B[mL/min/kg]
Irinotecan 0.37 1.00 1.00 10.0 3.00 6.15 10.6
APC 0.37 1.00 1.00 1.50 0.06 1.47 5.45
NPC 0.37 1.00 1.00 6.00 2.00 1.49 14.5
SN-38 0.05 1.00 1.00 2.00 0.70 9.91 103
SN-38G 1.00 1.00 1.00 2.80 0.08 1.44 2.03
KCZ 0.01 1.00 1.00 15.0 1.50 130 -
  1. Blood unbound fraction (f B ) values for irinotecan and SN-38 were obtained from the published paper by Oliver et al. [45]. The f B values for NPC and APC were assumed to be the same as that of Irinotecan. f B value for SN-38G was assumed to be 1.00. Urinary and biliary clearances (CLU,R, CLU,B) were defined for unbound blood concentration. CLU,Rand CLU,Bvalues for irinotecan, APC, SN-38, SN-38G were calculated using data from the publish paper [18]. Kp values were determined so that the simulation concentration/time profile fits to the experimental data from Slatter et al. [18].