TABLE 9.

Summary of emergent technologies applicable to research aimed at improving 8-aminoquinoline safety and efficacy^a

Technology	Platform	Capacity	Primary limitation	Reference(s)
In vitro hypnozoite development in primary human hepatocytes	384-well high-throughput system	Hypnozoitocidal efficacy of metabolized 8AQs and potentiation by partner drugs	Live P. vivax sporozoites, along with confirmed hepatic CYP2D6 phenotype, required	102, 306–310
In vivo hypnozoite development in humanized murine livers	Living humanized mice	Hypnozoitocidal efficacy of metabolized 8AQs and potentiation by partner drugs	Cost of the test animal, along with confirmed hepatic CYP2D6 phenotype required	311–313
In vitro metabolism of primaquine to active derivatives	Recombinant CYP2D6 systems, high throughput	Hemolytic toxicity assessment and ranking of 8AQs	Access to 8AQs other than primaquine and tafenoquine	101, 314, 315
In vivo or in vitro metabolism of primaquine to active metabolites	Ultra-HPLC quadrupole time of flight mass spectroscopy	Identifying relevant metabolites	Cost of instrumentation	80, 316
In vivo G6PD toxicity of 8AQs	Living humanized mice or zebra fish	Hemolytic toxicity across 8AQs and variants of G6PD deficiency	Cost of the test animal, along with confirmed hepatic CYP2D6 phenotype	69, 70

^a8AQ, 8-aminoquinoline; HPLC, high-performance liquid chromatography.