Table I.

Initial Range and Theoretical Lower Limit of Parameters for CNM

A. Common parameters
Parameter	Unit	Irinotecan	SN-38	SN-38G	NPC	APC	Theoretical lower limit
Vcentral	L/kg	0.075 ~ 0.75	0.075 ~ 0.75	0.075 ~ 0.75	0.075 ~ 0.75	0.075 ~ 0.75	0.074a
ka	/h	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0
kfeces	/h	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0
Rdif,h	-	-b,c	0.01 ~ 1.0	0.01 ~ 1.0	-c	-c	0
1/β	-	-b	1.1 ~ 10	1.1 ~ 10	1.1 ~ 10	1.1 ~ 10	1
CLint,all	L/h/kg	-b	0.1 ~ 100	0.1 ~ 100	0.1 ~ 100	0.1 ~ 100	0
1/fbile	-	-b	-e	-d	1.1 ~ 10	-d	1
kbile	/h	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0.06 ~ 6.0	0
Rdif,ent	-	0.1 ~ 10	0.1 ~ 10	0.1 ~ 10	-c	-c	0
B. Irinotecan parameters
Parameter	Unit	Value	Theoretical lower limit
PSdif,inf,h	L/kg	0.1 ~ 100	0
CLSN-38,h(irinotecan)	L/h/kg	0.1 ~ 100	0
CLNPC,h(irinotecan)	L/h/kg	0.1 ~ 100	0
CLAPC,h(irinotecan)	L/h/kg	0.1 ~ 100	0
CLothers,h(irinotecan)	L/h/kg	0.1 ~ 100	0
CLbile	L/h/kg	0.1 ~ 100	0
PSdif,eff,ent	L/h/kg	0.1 ~ 100	0
CLSN-38,h(irinotecan) /CLSN-38,ent(irinotecan)	-	1.1 ~ 10	1
CLNPC,h(irinotecan) / CLNPC,ent(irinotecan)	-	1.1 ~ 10	1
C. SN-38 parameters
Parameter	Unit	Value	Theoretical lower limit
1/fglu e	-	1.1 ~ 10	1
CLSN-38G,h(SN-38) /CLSN-38G,ent(SN-38)	-	1.1 ~ 10	1
D. SN-38G parameters
Parameter	Unit	Value	Theoretical lower limit
kdec	/h	0.06 ~ 6	0

^aV_central is larger than blood volume

^bHybrid parameters were not used. Instead of it, as shown in Table 1B. parameters for representing elementary steps were used

^cNo involvement of active uptake or efflux transporters for these compounds

^df_bile value was fixed as 1

^eThe ratio (f_glu) of metabolic clearance for glucuronidation of SN-38 to hepatic intrinsic clearance was estimated using the following equation, f_glu = 1 - f_blie