Lee Gayoung, Aneke Janessa Sochima, Sullivan David J
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Antimicrob Agents Chemother. 2025 Sep 3;69(9):e0024725. doi: 10.1128/aac.00247-25. Epub 2025 Jul 31.
Malaria drug interactions in cytostatic or inhibitory assays or suppression models can be different than curative killing interactions. In the pharmacodynamic high parasitemia ANKA-luciferase mouse blood-stage model, we investigated curative interaction analysis of multiple, daily dosed, short half-life, artesunate or single-dose, long half-life, pyronaridine against three single-dose, long half-life, quinolines-chloroquine, amodiaquine, and tafenoquine. Positive or negative parasiticidal activity measured by parasite reduction rate in the days post-treatment correlated nonspecifically to final curative interactions. Tafenoquine/artesunate and pyronaridine/amodiaquine also had fractional combination curative doses of 0.83 and 0.93, with the rest of the interactions closer to neutral at 0.9-1.1. All tested combinations are in the additive drug interaction range. Time to return of initial parasitemia in subcurative regimens was also imprecise for the prediction of cure with combinations. Short blood half-life azithromycin, requiring multiple daily doses, was additive to artesunate or pyronaridine in fractional curative dose combination killing. Murine malaria high parasitemia drug interactions at the curative metric are a potential benchmark for human studies.
在细胞生长抑制或抑制试验或抑制模型中，疟疾药物相互作用可能与治愈性杀灭相互作用不同。在药效学高疟原虫血症ANKA荧光素酶小鼠血液阶段模型中，我们研究了多日给药、半衰期短的青蒿琥酯或单剂量、半衰期长的咯萘啶对三种单剂量、半衰期长的喹啉类药物——氯喹、阿莫地喹和tafenoquine的治愈性相互作用分析。治疗后数天通过寄生虫减少率测量的阳性或阴性杀寄生虫活性与最终治愈性相互作用无特异性关联。tafenoquine/青蒿琥酯和咯萘啶/阿莫地喹的部分组合治愈剂量也分别为0.83和0.93，其余相互作用在0.9 - 1.1之间更接近中性。所有测试组合都在药物相加相互作用范围内。亚治愈方案中初始疟原虫血症恢复时间对于预测联合用药的治愈情况也不准确。需要每日多次给药的半衰期短的阿奇霉素在部分治愈剂量组合杀灭中与青蒿琥酯或咯萘啶相加。在治愈指标方面，小鼠疟疾高疟原虫血症药物相互作用是人体研究的潜在基准。
