Table 2.
SLA for the prediction of FE using the PBPK modeling approach
| Compound | Solubility | AUC ratio | Cmax ratio | Positive FE in vivo | Positive FE predicted by SLA | CYP3A4 or UGT substrate? | CL (l/h) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| FaSSIF (mg/ml) | Optimized (mg/ml) | Maximum (mg/ml) | Observed | Predicted | Observed | Predicted | |||||
| Carbamazepine | 0.3 | 0.85 | 1.8 | 1.12 | 1.08 | 1.35 | 1.21 | Yes | Yes | CYP3A4, UGT | 2.7 [50] |
| Efavirenz | 0.07 | 0.068 | 0.22 | 1.28 | 1.44 | 1.79 | 1.87 | Yes | Yes | CYP3A4 | 9.4 (po) [51] |
| Digoxin | 0.001 | 0.055 | 0.055 | 0.98 | 1 | 0.8 | 1 | No | No | No | 5.28 [51] |
| Mefenamic acid | 0.015 | 0.5 | 0.5 | 0.97 | 1 | 1.05 | 1 | No | No | No | 21.23 (po) [51] |
| Felodipine | 0.01 | 0.012 | * | 1.53 | * | 1.04 | * | No | * | CYP3A4 | 90 [47] |
| Clopidogrel | 0.017 | 0.06 | * | 9.2 | * | 6.5 | * | Yes | * | CYP3A4 | 84 [52] |
AUC area under the curve, Cmax maximum blood/plasma concentration, CL total body clearance value, CYP3A4 Cytochrome P450 3A4, FaSSIF fasted state simulated intestinal fluid solubility, Maximum solubility PBPK model hypothetical solubility that exceeds the optimized solubility that helps to identify SLA, Optimized solubility PBPK model hypothetical solubility beyond which there were no further changes between predicted and observed profile, PBPK physiologically based pharmacokinetic model, SLA solubility-limited absorption, UGT uridine diphosphate glucuronosyltransferase
*The value could not be determined