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 Parameter | Definition | TM | SFM |
|---|---|---|---|
| fQ | Fraction of QI to enterocyte region | 1 | 0.10 (11.7) |
| ka (min-1) | Absorption rate constant of morphine | 0.03 (12.6) | 0.028 (7.91) |
| Fabs | Fraction of dose absorbed in gut lumen | 0.90 (10.2) | 0.92 (10.7) |
 (ml·min-1) | Net influx clearance of morphine in the intestine | 0.821 (44.9) | 1.38 (49.2) |
 (ml·min-1) | Net efflux clearance of M in intestine | 5.99 (34.9) | 2.60 (39.9) |
 (ml·min-1) | Net influx clearance of M in liver | 15.0 (43.8) | 14.5 (17.6) |
 (ml·min-1) | Net efflux clearance of M in liver | 10.6 (10.0) | 5.90 (14.0) |
 (ml·min-1) | Metabolic intrinsic clearance of M forming MG in intestine | 3.14 (34.2) | 2.93 (22.9) |
 (ml·min-1) | Net intestinal intrinsic secretion clearance for M | 1.59 (9.92) | 2.09 (11.1) |
 (ml·min-1) | Metabolic intrinsic clearance of M forming MG in liver | 7.43 (16.5) | 3.73 (28.3) |
 (ml·min-1) | Metabolic intrinsic clearance of M forming other metabolites in liver | 0.35 (12.0) | 0.51 (21.4) |
 (ml·min-1) | Net biliary clearance of M | 0.06 (12.7) | 0.13 (18.8) |
 (ml·min-1) | Net renal clearance of M | 0.91 (54.5) | 1.27 (57.8) |
 (ml·min-1) | Renal clearance for M after correcting for  (Table 2) | 1.39 | 1.94 |
 (ml·min-1) | Efflux clearance for MG in the intestine | 4.09 (24.1) | 2.97 (4.7) |
 (ml·min-1) | Intestinal intrinsic secretion for MG | 0.22 (21.8) | 0.35 (11.4) |
 (ml·min-1) | Influx clearance for MG in the liver (assigned) | 1 | 1 |
 (ml·min-1) | Efflux clearance for MG in the liver | 0.04 (62.1) | 0.2 (56.8) |
 (ml·min-1) | Biliary clearance of MG | 0.29 (38.3) | 0.70 (43.5) |
 (ml·min-1) | Net renal clearance of MG | 2.40 (54.5) | 0.40 (48.3) |
 (ml·min-1) | Renal clearance for MG after correcting for  = 0.98 | 2.45 | 0.41 |
| AIC | Akaike information criteria | 317 | 308 |