Sinou V, Grellier P, Schrevel J
Laboratoire de Biologie Parasitaire, Muséum National d'Histoire Naturelle, Paris, France.
Antimicrob Agents Chemother. 1996 Feb;40(2):358-61. doi: 10.1128/AAC.40.2.358.
The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stage; an inhibition of more than 60% of parasite development was observed at 10 nM. At this drug concentration, the development of the younger ring and trophozoite forms was unaffected. The in vivo antimalarial activity of docetaxel against the development in blood of old trophozoites of a species that causes malaria in rodents, Plasmodium vinckei petteri, was evaluated in IOPS-OF1 mice. Two tests were performed: the 4-day suppressive test, as described by Peters (W. Peters, p. 145-273, in Chemotherapy, and Drug Resistance in Malaria, vol. 1, 1987), and the effects of a single injection of docetaxel after inoculation of the parasites. A single injection of docetaxel at 40 mg/kg of body weight was sufficient to reduce drastically the level of parasitemia; 90% inhibition of the development of parasites in blood was observed 5 days after drug injection. This program avoided the toxicity observed when mice were treated with four injections of docetaxel. The possibility of using a single bolus of taxoids to treat malaria infections is discussed.
通过让感染环状体、滋养体和裂殖体的红细胞暴露于不同浓度的多西他赛（泰索帝）5小时，评估恶性疟原虫对短期暴露于该药物的阶段依赖性易感性。结果表明，裂殖体阶段是最敏感的阶段；在10 nM时观察到超过60%的寄生虫发育受到抑制。在此药物浓度下，较年轻的环状体和滋养体形式的发育未受影响。在IOPS-OF1小鼠中评估了多西他赛对引起啮齿动物疟疾的物种——文氏疟原虫彼得亚种老龄滋养体血液发育的体内抗疟活性。进行了两项试验：如彼得斯所述的4天抑制试验（W. Peters，《疟疾的化疗和耐药性》第1卷，第145 - 273页，1987年），以及在接种寄生虫后单次注射多西他赛的效果。以40 mg/kg体重单次注射多西他赛足以显著降低疟原虫血症水平；在药物注射后5天观察到血液中寄生虫发育受到90%的抑制。该方案避免了小鼠接受四次多西他赛注射时所观察到的毒性。讨论了使用单次大剂量紫杉烷类药物治疗疟疾感染的可能性。
