当前位置： SCI文献检索 > Journal of Global Antimicrobial Resistance期刊下所有文献 > Investigation of pre-clinical pharmacokinetic parameters of atovaquone nanosuspension prepared using a pH-based precipitation method and its pharmacodynamic properties in a novel artemisinin combination.

Investigation of pre-clinical pharmacokinetic parameters of atovaquone nanosuspension prepared using a pH-based precipitation method and its pharmacodynamic properties in a novel artemisinin combination.

Abstract：

OBJECTIVES:Recently, a growing resistance to antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, artemisinin derivatives and mefloquine has been observed. The pharmacokinetic limitation of the current therapy and multi-drug resistance has resulted in an urgent need to study the new antimalarial combinations with existing drugs. This study investigated the activity of a novel triple combination of atovaquone (nanosized)-proguanil-artesunate as an alternative artemisinin combination therapy. Atovaquone in this combination was formulated as a freeze-dried nanosuspension and its pharmacokinetic parameters were also evaluated. METHODS:The suppressive and curative effect of atovaquone nanosuspension, proguanil, and artesunate were studied in a murine model. The in vivo pharmacokinetics of the newly developed atovaquone nanosuspension with particle size less than 200 nm was investigated. RESULTS:Prophylactic efficacy of atovaquone nanosuspension alone at 1/80th the therapeutic dose was proven. In the curative test, atovaquone nanosuspension and proguanil at 1/10th the therapeutic dose was the minimum effective dose that resulted in complete cure of parasitaemia. As a triple combination, atovaquone nanosuspension in combination with proguanil at 1/80th the therapeutic dose of each and 1/5th the therapeutic dose of artesunate resulted in a complete cure. The in vivo pharmacokinetics of the nanosuspension showed a significant (three times) reduction in Tmax value and the area under the curve of the nanosuspension was 1.9 times greater as compared with the plain suspension. CONCLUSIONS:The potential of the synergistic combination of atovaquone nanosuspension-proguanil-artesunate in curing the multi-drug resistant malarial infection at reduced doses of all three drugs could be a solution to pill burden observed with the current therapy.

journal_name

J Glob Antimicrob Resist

journal_title

Journal of global antimicrobial resistance

authors

Kathpalia H,Juvekar S,Mohanraj K,Apsingekar M,Shidhaye S

doi

10.1016/j.jgar.2020.02.018

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

248-256

eissn

2213-7165

issn

2213-7173

pii

S2213-7165(20)30047-3

journal_volume

22

pub_type

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