Tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines

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
1.8^a/35	None reported	Not described	NA	~ 50	1	[44]
12^b/3	None	None	6.7	124	2.5	[19, 20]
24^b/3	None	Vomiting, methemoglobinemia	13	284	5.7	[19, 20]
48—Non-Lethal^b/2	None	Methemoglobinemia	27	333	6.7	[19, 20]
48—Lethal^b/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

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