| dc.description |
: Tafenoquine (TQ), a new synthetic analog of primaquine, has relatively poor
bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD)-deficient
individuals. A microemulsion formulation of TQ (MTQ) with sizes 20 nm improved the
solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area
under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min⋅µmol/L) for reference TQ and
MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to
tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquinesensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half
maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent
activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in
toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby
report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages
of Plasmodium parasites without a corresponding increase in toxicity. |
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