TABLE 7

Additional parameters obtained from estimates in Table 5

Parameter	Definition	TM-PBPK	SFM-PBPK
	Ratio of effective uptake/efflux clearance of M in intestine, or intestine to blood partitioning of unbound morphine	0.137	0.531
	Ratio of effective uptake/efflux clearance of M in liver, or liver to blood partitioning ratio of unbound morphine	1.42	2.46
F_I	Intestinal availability of M	0.654	0.457

	^{^d}	0.629	0.282
F_L	Hepatic availability of M	0.574	0.574

	^{^d}	0.710	0.717
F_sys = F_abs * F_I * F_L	Systemic bioavailability:	0.334	0.242

		0.402	0.186
	Intestinal availability of MG	0.95	0.89

	Hepatic availability of MG	0.12	0.22

	Fraction of hepatic clearance of M forming MG	0.948	0.854

^{^a}	Fraction of total body clearance of M forming MG (note that f_e = 0.334 from Table 3)	0.631	0.569
^{^b}	Fractional contribution of intestine to intestinal-liver removal	0.460	0.093
		0.570^{^e}	0.171^{^e}
^{^c}	Fractional contribution of liver to intestinal-liver removal	0.540	0.907
		0.430^{^e}	0.829^{^e}