TABLE 7

Additional parameters obtained from estimates in Table 5

ParameterDefinitionTM-PBPKSFM-PBPK
Embedded ImageRatio of effective uptake/efflux clearance of M in intestine, or intestine to blood partitioning of unbound morphine0.1370.531
Embedded ImageRatio of effective uptake/efflux clearance of M in liver, or liver to blood partitioning ratio of unbound morphine1.422.46
FIIntestinal availability of M0.6540.457
Embedded Image
Embedded Imaged0.6290.282
FLHepatic availability of M0.5740.574
Embedded Image
Embedded Imaged0.7100.717
Fsys = Fabs * FI * FLSystemic bioavailability:0.3340.242
Embedded Image
Embedded Image0.4020.186
Embedded ImageIntestinal availability of MG0.950.89
Embedded Image
Embedded ImageHepatic availability of MG0.120.22
Embedded Image
Embedded ImageFraction of hepatic clearance of M forming MG0.9480.854
Embedded Image
Embedded ImageaFraction of total body clearance of M forming MG (note that fe = 0.334 from Table 3)0.6310.569
Embedded ImagebFractional contribution of intestine to intestinal-liver removal0.4600.093
0.570e0.171e
Embedded ImagecFractional contribution of liver to intestinal-liver removal0.5400.907
0.430e0.829e
  • a Based on definition of Pang and Kwan (1983).

  • b Calculated based on equations from Pang and Chow (2012): Embedded Image

  • c Calculated based on equations from Pang and Chow (2012): Embedded Image

  • d Equations from Pang and Sun (2010).

  • e FI and FL values, based on equations from Pang and Sun (2010).