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Malaria Research and Treatment Volume 2017 ,2017-04-13
Long-Term Prophylaxis and Pharmacokinetic Evaluation of Intramuscular Nano- and Microparticle Decoquinate in Mice Infected with P. berghei Sporozoites
Research Article
Qigui Li 1 Lisa Xie 1 Diana Caridha 1 Qiang Zeng 1 Jing Zhang 1 Norma Roncal 1 Ping Zhang 1 Chau Vuong 1 Brittney Potter 1 Jason Sousa 1 Sean Marcsisin 1 Lisa Read 1 Mark Hickman 1
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DOI:10.1155/2017/7508291
Received 2016-10-26, accepted for publication 2017-01-31, Published 2017-01-31
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摘要

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.

授权许可

Copyright © 2017 Qigui Li et al. 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

Diagrammatic sketch of the dosage regimens of the decoquinate (DQ) following single intramuscular injection in 2, 4, 6, and 8 weeks prior to an inoculation with 10,000 P. berghei sporozoites intravenously in female C3H mice (n=5).

Representative in vivo bioluminescent images of C3H mice shown at different time points after injection of 10,000 sporozoites. Rainbow images show the relative levels of luminescence ranging from low (blue), to medium (green), to high (yellow/red). Luminescence levels (photons/sec) of livers in whole mice at 24-, 48- (liver stage), and 72-hour (blood stage) time points following single intramuscular dosing treated with IM-DQ in macrosuspension at a MCD100 dose of 120 mg/kg 8 weeks prior to malaria infection (8 W, left) and oily vehicle control (VC, right) after sporozoite infection intravenously at day 0. Normally, P. berghei sporozoites reside in the mouse liver for 44–52 hours after infection (n=5).

Mean plasma concentration-time profiles of intramuscular-decoquinate (IM-DQ) in nanosuspension measured by LC/MS/MS (red square) and computer fitted curves by pharmacokinetic parameters following single intramuscular injection at 120 mg/kg in ICR mice with minimum inhibitory concentration (MIC) of 5.12 ng/mL. The concentration T > MIC is 624.25 hr (n=2).

Mean plasma concentration-time profiles of intramuscular-decoquinate (IM-DQ) in microsuspension measured by LC/MS/MS (red square) and computer fitted curves by pharmacokinetic parameters following single intramuscular injection at 120 mg/kg in ICR mice with minimum inhibitory concentration (MIC) of 5.12 ng/mL. The concentration T > MIC is 1,375.00 hr (n=3).

通讯作者

Qigui Li.Military Malaria Research Program, Walter Reed Army Institute of Research, Experimental Therapeutics Branch, Silver Spring, MD, USA, army.mil.qigui.li.civ@mail.mil

推荐引用方式

Qigui Li,Lisa Xie,Diana Caridha,Qiang Zeng,Jing Zhang,Norma Roncal,Ping Zhang,Chau Vuong,Brittney Potter,Jason Sousa,Sean Marcsisin,Lisa Read,Mark Hickman. Long-Term Prophylaxis and Pharmacokinetic Evaluation of Intramuscular Nano- and Microparticle Decoquinate in Mice Infected with P. berghei Sporozoites. Malaria Research and Treatment ,Vol.2017(2017)

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