TABLE 5

Fitted parameters for the PBPK models, with nested TM or SFM intestinal models, showing that SFM is the superior model

Values are presented as means ± CV%.

Fitted ParameterDefinitionTMSFM
fQFraction of QI to enterocyte region10.10 (11.7)
ka (min-1)Absorption rate constant of morphine0.03 (12.6)0.028 (7.91)
FabsFraction of dose absorbed in gut lumen0.90 (10.2)0.92 (10.7)
Embedded Image (ml·min-1)Net influx clearance of morphine in the intestine0.821 (44.9)1.38 (49.2)
Embedded Image (ml·min-1)Net efflux clearance of M in intestine5.99 (34.9)2.60 (39.9)
Embedded Image (ml·min-1)Net influx clearance of M in liver15.0 (43.8)14.5 (17.6)
Embedded Image(ml·min-1)Net efflux clearance of M in liver10.6 (10.0)5.90 (14.0)
Embedded Image (ml·min-1)Metabolic intrinsic clearance of M forming MG in intestine3.14 (34.2)2.93 (22.9)
Embedded Image(ml·min-1)Net intestinal intrinsic secretion clearance for M1.59 (9.92)2.09 (11.1)
Embedded Image(ml·min-1)Metabolic intrinsic clearance of M forming MG in liver7.43 (16.5)3.73 (28.3)
Embedded Image(ml·min-1)Metabolic intrinsic clearance of M forming other metabolites in liver0.35 (12.0)0.51 (21.4)
Embedded Image(ml·min-1)Net biliary clearance of M0.06 (12.7)0.13 (18.8)
Embedded Image (ml·min-1)Net renal clearance of M0.91 (54.5)1.27 (57.8)
Embedded Image (ml·min-1)Renal clearance for M after correcting for Embedded Image (Table 2)1.391.94
Embedded Image (ml·min-1)Efflux clearance for MG in the intestine4.09 (24.1)2.97 (4.7)
Embedded Image (ml·min-1)Intestinal intrinsic secretion for MG0.22 (21.8)0.35 (11.4)
Embedded Image (ml·min-1)Influx clearance for MG in the liver (assigned)11
Embedded Image (ml·min-1)Efflux clearance for MG in the liver0.04 (62.1)0.2 (56.8)
Embedded Image (ml·min-1)Biliary clearance of MG0.29 (38.3)0.70 (43.5)
Embedded Image (ml·min-1)Net renal clearance of MG2.40 (54.5)0.40 (48.3)
Embedded Image (ml·min-1)Renal clearance for MG after correcting for Embedded Image= 0.982.450.41
AICAkaike information criteria317308