Abstract
Decoquinate nanoparticle and microparticle suspended in an oily vehicle to retard drug release are evaluated for long-term malaria prophylaxis. Pharmacokinetic studies in normal animals and antimalarial efficacy in liver stage malaria mice were conducted at various single intramuscular-decoquinate doses for 2, 4, 6, or 8 weeks prior to infection with P. berghei sporozoites. The liver stage efficacy evaluation was monitored by using an in vivo imaging system. Full causal prophylaxis was shown in mice with a single intramuscular dose at 120 mg/kg of nanoparticle decoquinate (0.43 μm) for 2-3 weeks and with microparticle decoquinate (8.31 μm) injected 8 weeks earlier than inoculation. The time above MIC of 1,375 hr observed with the microparticle formulation provided a 2.2-fold longer drug exposure than with the nanoparticle formulation (624 hr). The prophylactic effect of the microparticle formulation observed in mice was shown to be 3-4 times longer than the nanoparticle decoquinate formulation.
Highlights
Decoquinate (DQ) is a 4-hydroxy quinoline compound that has been used as an anticoccidial drug in livestock such as cattle, sheep, and chicken, for many years without any signs of adverse effects
IM-DQ in nano- and microsuspensions was prepared by the procedure involving oily dispersion of the drug with particle size reduction by sonication or high-pressure homogenizer
The results showed that none of the preparations showed a changed in the DQ chromatography profile, suggesting the chemical structure of DQ was unaltered
Summary
Decoquinate (DQ) is a 4-hydroxy quinoline compound that has been used as an anticoccidial drug in livestock such as cattle, sheep, and chicken, for many years without any signs of adverse effects. DQ kills developing gametocytes, the parasite stage responsible for malaria transmission. Decoquinate is structurally distinct to atovaquone, which is broadly used for malaria prophylaxis and treatment, and decoquinate demonstrates limited cross-resistance to atovaquone-resistant parasites [3]. Oral administration of a single dose of DQ has been shown to be effective as a prophylactic antimalarial drug, which reinforces the hypothesis that DQ is worthy of further development as an antimalarial in man [4]. Despite the demonstrated efficacy of DQ against malaria, it has never been clinically developed for use in man likely due to the very poor solubility and permeability of this compound
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