PBPK model parameter estimates after a single subcutaneous dose of 50-mg/kg PNL in rats
| Parameter (Unit) | Definition | Estimate (CV%) |
|---|---|---|
| NCPC (ng/ml) | Binding capacity of CBG | 297.8 (Fixed) |
| KC (ml/ng) | Association constant of CBG | 0.0046 (Fixed) |
| NAPA (ng/ml) | Binding capacity of albumin | 164,342 (Fixed) |
| KA (ml/ng) | Association constant of albumin | 1.02 × 10−5 (Fixed) |
| Bmax1 (ng/ml) | Binding capacity of muscle | 690.5 (12.5) |
| Bmax2 (ng/ml) | Binding capacity of liver, heart, intestine, bone | 188.5 (11.6) |
| Bmax3 (ng/ml) | Binding capacity of kidney, lung, skin, spleen, fat, brain | 50.77 (10.8) |
| Kd (ng/ml) | Dissociation constant for PNL-tissue interaction | 3.01 (23.8) |
| ka (h−1) | Subcutaneous first-order absorption rate constant | 2.59 (5.1) |
| CLint (ml/h) | CBG-free hepatic intrinsic clearance | 1789 (16.3) |
| CLk (ml/h) | CBG-free renal clearance | 191.2 (40.3) |
| CLup (ml/h) | Brain bidirectional uptake clearance | 0.13 (22.6) |
| CLeff (ml/h) | Brain unidirectional efflux clearance | 4.58 (25.9) |
| fm_liver | Metabolite/drug ratio of PN/PNL for liver | 0.01 (30.1) |
| RB a | Blood-to-plasma conc. ratio | 0.71 (Fixed) |
↵a RB was estimated by Orthogonal Regression according to eq. 1.