Table 1. In vitro ADME for compounds 4 and 5 and drug controls.
| Compound | Solubilitya (μM) |
PAMPAa (10-5cm/s) | Caco-2a (A→B) (10-5cm/s) |
Caco-2a (B→A) (10-5cm/s) |
Caco-2a (ratio) | Gastric Stability t1/2 (h) |
Microsomal stability t½ (h) |
|---|---|---|---|---|---|---|---|
| 4 | 67 | 37.5 | 4.90 ± 0.03 | 3.90 ± 0.07 | 0.80 | > 48 | Mouse >4 Rat >4 Human > 4 |
| 5 | 0.3 | 23.7 | 1.68 ± 0.24 | 3.22 ± 0.29 | 1.92 | > 24 | Mouse >4 Rat >4 Human > 4 |
| carbamazepine | 82.2 | 9.56 | 7.18 ± 0.12 | 5.65 ± 0.32 | 0.79 | > 24 | Mouse >4 Rat >4 Human > 4 |
| digoxin | 80.3 | ND | 0.461 ± 0.046 | 2.71 ± 0.21 | 5.87 | > 24 | Mouse >4 Rat >4 Human > 4 |
| albendazole | 3.8 | 20.4 | ND | ND | ND | > 24 | Mouse 0.7±0.04 Rat 1.62±0.11 Human > 4 |
| verapamil | 70.0 | 150 | ND | ND | ND | > 24 | Mouse 0.8±0.1 Rat 0.4±0.8 Human 0.6±0.1 |
aExperiments performed at pH 7.4. Microsomal stability was tested at 20 μM. Data for Caco-2 experiments represent the mean ± the standard deviations for three separate runs. The numbers for PAMPA and Caco-2 assays represent permeability coefficients. Results reported as means and standard deviations represent 3 replicate experiments. ND indicates not determined.