Table 4.
Neurologic safety windows of various doses of tafenoquine in Rhesus monkeys
| Tafenoquine dose administered (mg/kg/)/N | Neurologic signs | Other clinical signs | Neurologic therapeutic index (ratio relative to effective dose based on dose administered)c | Cmax (ng/ml) | Neurologic therapeutic index (ratio relative to effective dose based on exposure) | Source |
|---|---|---|---|---|---|---|
| 1.8a/35 | None reported | Not described | NA | ~ 50 | 1 | [44] |
| 12b/3 | None | None | 6.7 | 124 | 2.5 | [19, 20] |
| 24b/3 | None | Vomiting, methemoglobinemia | 13 | 284 | 5.7 | [19, 20] |
| 48—Non-Lethalb/2 | None | Methemoglobinemia | 27 | 333 | 6.7 | [19, 20] |
| 48—Lethalb/2 | No pathological changes in CNS at autopsy | Vomiting, poor appetite, listlessness, depression, death, hepatotoxicity (amongst other findings noted on necropsy) | 27 | 551 | 11 | [19, 20] |
N number of animals
aAdministered as three equal divided doses over three days. This is the 95% curative dose of tafenoquine for radical cure of P. cynomolgi in Rhesus monkeys in combination with blood schizonticidal drugs
bAdministered as four equal divided doses over four days
cCalculated by dividing the total dose administered in column 1, rows 2, 3 or 4, by the 95% curative dose (1.8 mg/kg) listed in row 1 of column 1