Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University, 725 North Wolfe Street, Baltimore, MD, 21205, USA.
The Johns Hopkins Malaria Research Institute, Baltimore, MD, 21205, USA.
Nat Commun. 2018 Jan 22;9(1):315. doi: 10.1038/s41467-017-02603-z.
Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml and is causal, attributable to drug activity against liver stage parasites. Parasites that appear after subtherapeutic doses remain atovaquone-sensitive. Pharmacokinetic-pharmacodynamic analysis indicates protection can translate to humans at clinically achievable and safe drug concentrations, potentially offering protection for at least 1 month after a single administration. These findings support the use of long-acting injectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.
化学预防是目前预防疟疾的最佳方法，但由于不遵守药物治疗，其效果受到影响。在这里，我们开发了一种阿托伐醌固体药物纳米颗粒的长效注射制剂，该制剂可在 C57BL/6 小鼠中提供针对伯氏疟原虫 ANKA 疟疾的长期预防作用。在血浆浓度高于 200ng/ml 时即可获得保护，并且是因果关系，归因于药物对肝期寄生虫的活性。低于治疗剂量出现的寄生虫仍然对阿托伐醌敏感。药代动力学-药效学分析表明，在临床可达到的安全药物浓度下，这种保护作用可以转化为人类，单次给药后至少可以提供 1 个月的保护。这些发现支持使用长效注射制剂作为旅行者疟疾预防和现场疟疾控制的新方法。
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