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

Table 2 Neurologic toxicity of 8AQs in Rhesus monkeys

8AQ	MND (mg/kg)	Clinical neurologic signs	Onset of neurologic symptoms (Days)	Dose-limiting toxicity	MED (CD90 in mg/kg)	Neurologic therapeutic index (NTI)
Primaquine	168	None	NA	Malaise, weight loss, leucopenia, hepatotoxicity, methemoglobinemia	7.7	21
Pamaquine	60	None	≤ 7	Cyanosis, methemoglobinemia	14	4.3
Pentaquine	168	Postural hypotension	≤ 12	Cyanosis, methemoglobinemia	~ 45	3.7
Plasmocid	6	Nystagmus, loss of pupillary reflex, equilibrium and motor control	≤ 2	Neurotoxicity^a	Assume 7.7	< 1

Data from [1,2,3, 22]
MED refers to the minimum effective dose for radical cure of P. cynomolgi in Rhesus monkeys in combination with a blood schizonticide
All doses are the cumulative dose, i.e. the mg/kg/day × number of days dosed
MND the minimum cumulative neurotoxic dose causing neurodegeneration or neurologic clinical signs, NA not appilicable, NTI neurologic therapeutic index
NTI = MND/MED
^aSame neurologic signs as outlined in Column 3

ISSN: 1475-2875