Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
J Antimicrob Chemother. 2023 Oct 3;78(10):2406-2418. doi: 10.1093/jac/dkad260.
Pyronaridine-artesunate was recently strongly recommended in the 2022 update of the WHO Guidelines for the Treatment of Malaria, becoming the newest artemisinin-based combination therapy (ACT) for both uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Pyronaridine-artesunate, available as a tablet and paediatric granule formulations, is being adopted in regions where malaria treatment outcome is challenged by increasing chloroquine resistance. Pyronaridine is an old antimalarial agent that has been used for more than 50 years as a blood schizonticide, which exerts its antimalarial activity by interfering with the synthesis of the haemozoin pigment within the Plasmodium digestive vacuole. Pyronaridine exhibits a high blood-to-plasma distribution ratio due to its tendency to accumulate in blood cells. This feature is believed to play a crucial role in its pharmacokinetic (PK) properties and pharmacological activity. The PK characteristics of pyronaridine include rapid oral absorption, large volumes of distribution and low total body clearance, resulting in a long terminal apparent half-life. Moreover, differences in PK profiles have been observed between healthy volunteers and malaria-infected patients, indicating a potential disease-related impact on PK properties. Despite a long history, there is only limited knowledge of the clinical PK and pharmacodynamics of pyronaridine, particularly in special populations such as children and pregnant women. We here provide a comprehensive overview of the clinical pharmacology of pyronaridine in the treatment of malaria.
派隆那林-青蒿琥酯最近在世界卫生组织 2022 年疟疾治疗指南更新版中被强烈推荐，成为治疗无并发症恶性疟原虫和间日疟原虫疟疾的最新青蒿素为基础的联合治疗药物（ACT）。派隆那林-青蒿琥酯有片剂和儿科颗粒剂两种剂型，在氯喹耐药性增加导致疟疾治疗效果受到挑战的地区得到采用。派隆那林是一种古老的抗疟药物，作为一种血裂殖体杀灭剂，已经使用了 50 多年，通过干扰疟原虫消化空泡内的血红素合成发挥抗疟作用。派隆那林由于倾向于在血细胞中积累，因此具有较高的血/血浆分配比。这种特性被认为在其药代动力学（PK）特性和药理活性中发挥着关键作用。派隆那林的 PK 特征包括快速口服吸收、大的分布容积和低的总体清除率，导致较长的终末表观半衰期。此外，在健康志愿者和疟疾感染患者之间观察到 PK 谱的差异，表明 PK 特性可能受到疾病的影响。尽管历史悠久，但人们对派隆那林的临床 PK 和药效动力学的了解非常有限，特别是在儿童和孕妇等特殊人群中。我们在此全面概述了派隆那林在治疗疟疾中的临床药理学。
