Table 5 Estimated solubility limited absorbable dose (SLAD)
From: An in vitro toolbox to accelerate anti-malarial drug discovery and development
Compound | Permeability | Solubility/dose | |||
|---|---|---|---|---|---|
Predicted human Peff (10−4 cm/s) | Permeability classificationa | An | Ssi (µg/mL) | SLAD (mg) | |
Ionized or partially ionized bases at physiological pH | |||||
 Doxycyclin | 0.70 | Intermediate | 1.0 | > 2000 | > 1000 |
 Pyronaridine | 1.4 | High | 1.6 | > 2000 | > 1610 |
 Proguanil | 0.71 | Intermediate | 1.0 | > 2000 | > 1000 |
 Primaquine | 3.0 | High | 3.6 | > 2000 | > 3560 |
 Chloroquine | 1.4 | High | 1.6 | > 2000 | > 1620 |
 Chlorproguanil | 1.5 | High | 1.8 | 1100 | 998 |
 Azithromycin | 0.16 | Low | 1.0 | 1440 | 720 |
 AQ-13 | 1.9 | High | 2.2 | > 2000 | > 2250 |
 Quinine | 3.7 | High | 4.4 | 1960 | 4280 |
 Clindamycin | 2.1 | High | 2.5 | > 2000 | > 2530 |
 KAF156 | 2.9 | High | 3.5 | 1600 | 2780 |
 M5717 | 3.4 | High | 4.0 | > 3000 | > 6050 |
 OZ277 | 2.7 | High | 3.2 | > 2000 | > 3240 |
 Mefloquine | 7.7 | High | 9.2 | 584 | 2690 |
 Amodiaquine | 4.7 | High | 5.6 | 1120 | 3130 |
 Ferroquine | 2.2 | High | 2.7 | 320 | 426 |
 Naphthoquine | 9.2 | High | 11 | 410 | 2250 |
 Tafenoquine | 11 | High | 13 | 15.8 | 105 |
 MMV253 | 6.8 | High | 8.1 | 569 | 2300 |
 MMV052 | 11 | High | 13 | 1140 | 7580 |
 Piperaquine | 11 | High | 13 | 103 | 685 |
 Halofantrine | 11 | High | 13 | 69.9 | 466 |
 TDD-E209 | 11 | High | 13 | 87.0 | 579 |
 Lumefantrine | CND | CND | CND | CND | CND |
Ionized acids at physiological pH | |||||
 Sulfadoxine | 1.9 | High | 2.2 | 858 | 959 |
 Sulfamethoxazole | 0.85 | Intermediate | 1.0 | > 2000 | > 1000 |
 Artesunate | 0.66 | Intermediate | 1.0 | 1690 | 845 |
 Atovaquone | 11 | High | 13 | 1.83 | 12 |
Zwitterionic or partially zwitterionic at physiological pH | |||||
 P218 | 0.24 | Low | 1.0 | 408 | 204 |
 JPC3210 | 11 | High | 13 | 7.60 | 51 |
Neutral at physiological pH | |||||
 Dapsone | 4.1 | High | 4.9 | 323 | 786 |
 Dihydroartemisinin | 4.4 | High | 5.2 | 159 | 413 |
 DSM421 | 3.3 | High | 3.9 | 93.0 | 182 |
 Pyrimethamine | 4.9 | High | 5.9 | 111 | 326 |
 MMV048 | 3.8 | High | 4.5 | 6.70 | 15 |
 Artemisone | 5.0 | High | 6.0 | 115 | 345 |
 Artemether | 3.9 | High | 4.7 | 166 | 388 |
 SJ733 | 1.8 | High | 2.2 | 101 | 109 |
 DSM265 | 4.8 | High | 5.7 | 5.10 | 14 |
 KAE609 | 11 | High | 13 | 111 | 738 |
 OZ439 | 11 | High | 13 | 40.6 | 270 |
 ELQ300 | 11 | High | 13 | 0.520 | 3 |