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

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

Compound	f _B	Kp _GI	Kp _Liver	Kp _Adipose	Kp _NET	CL_U,R[mL/min/kg]	CL_U,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	-

Blood unbound fraction (f_B) values for irinotecan and SN-38 were obtained from the published paper by Oliver et al. [45]. The f_Bvalues for NPC and APC were assumed to be the same as that of Irinotecan. f_Bvalue for SN-38G was assumed to be 1.00. Urinary and biliary clearances (CL_U,R, CL_U,B) were defined for unbound blood concentration. CL_U,Rand CL_U,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].

ISSN: 1471-2105