Table 4 Caco-2 mass balance and bidirectional permeability coefficients
From: An in vitro toolbox to accelerate anti-malarial drug discovery and development
Compound | Matrix | A–B mass bal (%) | A–B P aapp (10−6 cm/s) | B–A mass bal (%) | B–A P aapp (10−6 cm/s) | Efflux ratio |
|---|---|---|---|---|---|---|
Ionized or partially ionized bases at physiological pH | ||||||
 Cycloguanil | Buffer | 100 | 1.2 ± 0.070 | 100 | 0.77 ± 0.05 | 0.7 |
 Doxycyclin | Buffer | 99 | 3.4 ± 0.23 | 110 | 4.2 ± 0.29 | 1.2 |
 Pyronaridine | Plasma | 63 | 16 ± 2.2 | 87 | 41 ± 3.0 | 2.6 |
 Proguanil | Buffer | 82 | 3.5 ± 0.75 | 95 | 7.9 ± 0.51 | 2.3 |
 Primaquine | Buffer | 66 | 29 ± 4.5 | 99 | 34 ± 1.5 | 1.2 |
 Chloroquineb | Plasma | 61 | 16 ± 2.5 | 110 | 22 ± 4.6 | 1.4 |
 Chlorproguanil | Plasma | 79 | 19 ± 3.0 | 100 | 61 ± 7.4 | 3.2 |
 Azithromycin | Buffer | 98 | 0.37, 0.38 | 87 | 13 ± 3.9 | 33 |
 AQ-13 | Plasma | 54 | 25 ± 2.3 | 92 | 32 ± 0.8 | 1.2 |
 Quinineb | Buffer | 70 | 39 ± 5.0 | 92 | 40 ± 4.5 | 1.0 |
 Clindamycin | Buffer | 75 | 17 ± 1.1 | 92 | 48 ± 9.1 | 2.8 |
 KAF156 | Plasma | 86 |  47 ± 7.6 | 96 | 230 ± 17 | 4.9 |
 M5717 | Buffer | 60 | 34 ± 2.6 | 81 | 39 ± 7.6 | 1.1 |
 OZ277 | Plasma | 67 | 42 ± 2.8 | 100 | 70 ± 0.38 | 1.7 |
 Mefloquineb | Plasma | 70 | 180 ± 20 | 86 | 150 ± 10 | 0.83 |
 Amodiaquineb | Plasma | 81 | 90 ± 8.3 | 88 | 63 ± 9.6 | 0.7 |
 NPC1161B | Plasma | 76 | > 300 | 97 | > 300 | – |
 Ferroquine | Plasma | 66 | 32 ± 6.8 | 110 | 24 ± 4.1 | 0.8 |
 Naphthoquineb | Plasma | 72 | 230 ± 32 | 94 | 180 ± 10 | 0.78 |
 Tafenoquine | Plasma | 79 | > 300 | 110 | v300 | – |
 MMV253 | Plasma | 84 | 150 ± 29 | 94 | 150 ± 23 | 1.0 |
 MMV052 | Plasma | 77 | > 300 | 110 | > 300 | – |
 Piperaquineb | Plasma | 100 | > 300 | 100 | > 300 | – |
 Halofantrineb | Plasma | 83 | > 300 | 87 | > 300 | – |
 TDD-E209 | Plasma | 93 | > 300 | 100 | > 300 | – |
 Lumefantrine | Plasma | 110 | CND | 110 | CND | CND |
Ionized acids at physiological pH | ||||||
 Sulfadoxine | Buffer | 93 | 15 ± 2.5 | 110 | 23 ± 2.8 | 1.6 |
 Sulfamethoxazole | Buffer | 96 | 4.5 ± 0.29 | 100 | 5.9 ± 0.26 | 1.3 |
 Artesunate | Buffer | 81 | 3.4, 2.9 | 84 | 2.8 ± 0.48 | 0.9 |
 Atovaquone b | Plasma | 99 | > 300 | 97 | > 300 | – |
Zwitterionic or partially zwitterionic at physiological pH | ||||||
 P218 | Buffer | 96 | 0.71 ± 0.04 | 100 | 15 ± 1.7 | 21 |
 JPC3210 | Plasma | 97 | > 300 | 100 | > 300 | – |
Neutral at physiological pH | ||||||
 Dapsone | Buffer | 86 | 45 ± 7.3 | 98 | 56 ± 1.3 | 1.2 |
 Dihydroartemisinin | Buffer | 85 | 50 ± 2.3 | 91 | 49 ± 1.2 | 1.0 |
 DSM421c | Buffer | 70 | 33 ± 2.5 | 98 | 46 | 1.4 |
 Pyrimethamine | Buffer | 75 | 60 ± 5.6 | 100 | 59 ± 2.9 | 1.0 |
 MMV048 | Buffer | 82 | 41 ± 2.1 | 98 | 53 ± 1.9 | 1.3 |
 Artemisone | Buffer | 98 | 58.8, 64.5 | 99 | 47 ± 1.7 | 0.8 |
 Artemether | Buffer | 73 | 39.1, 46.3 | 95 | 42 ± 5.6 | 1.0 |
 SJ733 | Buffer | 93 | 14.0, 13.4 | 99 | 50 ± 2.0 | 3.6 |
 DSM265 | Buffer | 83 | 52.4, 69.7 | 93 | 49 ± 5.1 | 0.9 |
 KAE609 | Plasma | 93 | > 300 | 98 | > 300 | – |
 OZ439 | Plasma | 91 | > 300 | 110 | > 300 | – |
 ELQ300 | Plasma | 99 | > 300 | 110 | > 300 | – |