Table I.
Summary of the Food Effect Direction, Dose at Observed Food Effect, and Physicochemical and Absorption Properties of the 30 Modeled Compounds
| Compound | Maximum dose in food effect study | Food effect | Molecular weight1 (g/mol) | cLogD2 | pKa | Apparent permeability (× 10−6 cm/s) | Effective permeability (× 10−4 cm/s)3 | Solubility at pH 6.5 (μg/ml) | FaSSIF solubility (μg/ml) | FeSSIF solubility (μg/ml) | BCS | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alectinib | 600 | Positive | 482.6 | 4.8 | 7.05b | n/a | 2.5^ | 23 | 77 | II | (11) | |
| Amiodarone | 600 | Positive | 645.3 | 6.5 | 5.90b | n/a | 0.9^ | 2 | 472 | 784 | II | (12) |
| Aprepitant | 100 | Positive | 534.4 | 5.2 | 2.45b, 9.15a | 13 (MDCK) | 2.4 | 0.7 | 5.4 | 92.4 | II/IV | (13,14) |
| Cimetidine | 200 | None | 252.3 | − 0.2 | 6.90b | 5.4 (Caco-2)^ | 1.278 | 22,000 | 21,500 | III | Simcyp value for Peff | |
| Clarithromycin | 500 | None | 748.0 | 2.2 | 8.99b | 5 (MDCK) | 0.3 | 132 | 1656 | II | ||
| Dabrafenib | 150 | Negative | 519.6 | 4.6 | 2.2b, 6.6a | 84 (MDCK) | 5.5 | 1 | 6.2^ | 6.8^ | II | (15) |
| Danazol | 100 | Positive | 337.5 | 3.5 | Neutral | 4.2 (MDCK) | 1.0^ | 0.69 | 7270 | 52,600 | II | (16–18) |
| Danirixin | 50 | Negative | 441.9 | 1.8 | 4.80a, 8.10b | n/a | 0.9^ | 459 | 724 | II | GSK in-house data | |
| d-Sotalol | 160 | None | 272.4 | − 2.1 | 8.28a, 9.72b | n/a | 1.2^ | 15,800^ | n/a | n/a | III | (19) |
| Etoricoxib | 120 | Negative | 358.8 | 2.8 | 4.5b | 52.3 (Caco-2)^ | 4.8 | 67^ | 67^ | 95^ | II | (20) |
| Fluoxetine HCl | 40 | None | 309.3 | 1.8 | 9.8b | 1.69 (MDCK) | 1.0^ | 1533 | 6400 | 1720 | I | |
| Furosemide | 40 | Negative | 330.7 | − 1.3 | 3.9a | n/a | 0.5^ | 5188^ | 3201^ | 684^ | IV | (21–23) |
| Imatinib | 400 | None | 493.6 | 3.5 | 3.73b, 8.07b | 4.7 (MDCK) | 1.1 | 113 | 220^ | 2210^ | II | (24) |
| Isoniazid | 300 | Negative | 137.1 | − 0.7 | 1.80b, 3.50b | 16 (Caco-2)^ | 4.0 | 128,000 | n/a | n/a | I | (25) |
| Itraconazole | 100 | Positive | 705.6 | 7.3 | 4.28b | n/a | 9.9 | 1120 | 3620 | II | ||
| Ivacaftor | 150 | Positive | 392.5 | 4.3 | 9.40a, 11.60a | 11.9 (Caco-2)^ | 1.2 | 0.5^ | 53^ | 550^ | II/IV | Vertex in-house data |
| Metoprolol | 100 | Positive | 267.4 | − 0.5 | 9.75b | n/a | 1.3^ | 17,100 | n/a | n/a | I | (26) |
| Nefazodone HCl | 200 | Negative | 470.0 | 4.5 | 6.50b | 11 (Caco-2) ^ | 2.2 | 5378 | 1393 | 3100 | II | |
| Nelfinavir mesylate | 1250 | Positive | 567.8 | 4.1 | 6.0b | 1.3 (MDCK) | 0.7 | 41.4^ | 22^ | 243^ | II/IV | (27,28) |
| Nifedipine | 10 | None | 346.3 | 1.8 | Neutral | 23.5 (Caco-2)^ | 12.5 | 9.2^ | 17.1^ | 56.2^ | II | (29,30) |
| Oseltamivir | 150 | None | 312.4 | − 0.7 | 7.70b | n/a | 1.5^ | 25,000^ | n/a | n/a | III | (31) |
| Panobinostat | 20 | None | 349.4 | 0.7 | 8.35a, 9.0b | 11 (Caco-2)^ | 2.3 | 261^ | 140^ | 230^ | II | Novartis in-house data |
| Pazopanib | 800 | Positive | 437.5 | 3.5 | 2.1b, 6.4b | 16.9 (Caco-2)^ | 2.3 | 0.5 | 1.2 | 2.8 | II/IV | (32) |
| Phenytoin | 300 | Positive | 252.3 | 1.2 | 8.06a | 51 (MDCK) | 4.0 | 31^ | 39.6^ | 49.5^ | II | (33) |
| Telaprevir | 750 | Positive | 679.8 | 2.6 | Neutral | 4.4 (Caco-2)^ | 1.4 | 85 | 120 | 80 | II | Vertex in-house data |
| Tezacaftor | 50 | None | 520.5 | 3.4 | Neutral | 4.2 (Caco-2)^ | 2.5 | 110^ | 119^ | 4783^ | II | Vertex in-house data |
| Trospium IR | 30 | Negative | 392.5 | − 0.5 | +Charged | n/a | 0.1 (0.005 to 0.5) | 780 | n/a | n/a | III | (34,35) |
| Trospium XR | 60 | Negative | 392.5 | − 0.5 | +Charged | 0.1 (0.005 to 0.5) | 780 | n/a | n/a | III | ||
| Venetoclax | 100 | Positive | 868.4 | 6.5 | 3.40a; 10.3b | n/a | 1.0^ | 6 | 0.0337 | 26.4 | IV | (7) |
| Zidovudine | 300 | Negative | 267.2 | − 0.4 | 9.70b | n/a | 3.7^ | > 10 | > 10,000 | III | ||
| Ziprasidone HCl | 80 | Positive | 412.9 | 4.1 | 6.58b | 12.3 (Caco-2)^ | 2.3 | 1 | 4 | 13 | II | (36) |
For highly soluble and/or hydrophilic compounds, the impact of bile salts on the solubility was considered negligible and FaSSIF/FeSSIF data was not reported
n/a, not available
1Molecular weight of active ingredient only. The counterion of salts is excluded from the molecular weight
2Log10 of the octanol/water distribution coefficient at pH 7.4 as calculated with the OpenEye software
2Effective jejunum permeability used in the PBPK model
^Data was not generated within this working group. Source of data provided in the reference column