Table 3.
Assessment of the physiologically-based tubular reabsorption model for prediction of CLR. Performance of the mechanistic model was assessed initially for all drugs with a measured Caco-2 Papp value with the exception of those that showed evidence of net secretion (clearance ratio > 1.5). Subsequently, the tubular reabsorption model was reassessed after excluding drugs currently identified as substrates for drug transporters expressed within kidney.
| R2 | # (%) of drugs within 3-fold of observed CLR | gmfe | RMSE | |
|---|---|---|---|---|
| CLR,filt only | ||||
| All drugs (45) | 0.38 | 26 (58%) | 3.73 | 43.0 |
| Neutral (15) | 0.15 | 5 (33%) | 6.69 | 63.4 |
| Acid (5) | 0.75 | 1 (20%) | 16.45 | 18.0 |
| Basic (16) | 0.84 | 14 (88%) | 1.80 | 18.0 |
| Zwitterion (8) | 0.41 | 5 (63%) | 2.47 | 44.9 |
| Amphoteric (1) | N/A | 1 (100%) | 1.02 | 2.3 |
| Minimal model | ||||
| All drugs (45) | 0.76 | 39 (87%) | 1.96 | 20.9 |
| Neutral (15) | 0.86 | 13 (87%) | 1.86 | 10.4 |
| Acid (5) | 0.84 | 4 (80%) | 2.29 | 2.1 |
| Basic (16) | 0.79 | 14 (88%) | 2.18 | 31.0 |
| Zwitterion (8) | 0.84 | 7 (88%) | 1.73 | 18.3 |
| Amphoteric (1) | N/A | 1 (100%) | 1.03 | 3.3 |
| Non-substrates of renal transporters (29) | 0.65 | 25 (86%) | 2.07 | 19.3 |
| Neutral (10) | 0.95 | 8 (80%) | 1.88 | 7.2 |
| Acid (5) | 0.84 | 4 (80%) | 2.29 | 2.1 |
| Basic (13) | 0.76 | 12 (92%) | 2.19 | 28.0 |
| Zwitterion (1) | N/A | 1 (100%) | 1.66 | 3.0 |
| Amphoteric (0) | N/A | N/A | N/A | N/A |