Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats.
Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats.
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雾化伊维菌素用于COVID-19和其他呼吸道疾病，概念验证，大鼠剂量范围研究。
DOI：
10.1038/s41598-020-74084-y
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发表时间：
2020-10-13
影响因子：
4.6
通讯作者：
Gil AG
中科院分区：
文献类型：
--
作者：
Chaccour C;Abizanda G;Irigoyen-Barrio Á;Casellas A;Aldaz A;Martínez-Galán F;Hammann F;Gil AG
伊维菌素是一种广泛使用的抗寄生虫药物，已知对多种单株 RNA 病毒有效。最近的数据显示，伊维菌素浓度可显着减少体外 SARS-CoV-2 的复制，而口服安全剂量无法达到这一浓度。吸入疗法已成功用于其他抗寄生虫药。使用能够递送具有肺泡沉积的颗粒的喷雾器，对 14 只大鼠施用基于乙醇的伊维菌素制剂一次。大鼠被随机分为三个目标剂量组：较低剂量（80-90 mg/kg）、较高剂量（110-140 mg/kg）或仅乙醇载体。进行毒理学分析，包括行为和体重监测、全血细胞计数、生物化学、尸检和肺部组织学检查。在所有动物中测定了伊维菌素在血浆和肺中的药代动力学特征。行为或体重没有相关变化。与横纹肌溶解症相容的肌肉酶出现延迟升高，这在对照组中也可见到，这归因于某些动物中乙醇剂量高达 11 g/kg。任何大鼠的肺部均未发现组织学异常。同一剂量组中，雄性动物接受了更高的伊维菌素剂量（根据脂肪重量调整），并且达到了比雌性更高的血浆浓度（平均 Cmax 为 86.2 ng/ml，较低剂量组为 26.2 ng/ml，平均 Cmax 为 152 ng/ml，较高剂量组为 51.8 ng/ml）。干预后 7 天，所有受试者肺部均检测到伊维菌素浓度，高剂量男性高达 524.3 ng/g，低剂量女性高达 27.3 ng/g。雾化伊维菌素可以在大鼠肺组织中达到药效浓度，需要额外的实验来评估该制剂在较大动物中的安全性。
Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80–90 mg/kg), higher dose (110–140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.
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影响因子：
158.5
作者：
Boulware, David R.;Pullen, Matthew F.;Hullsiek, Kathy H.
通讯作者：
Hullsiek, Kathy H.
影响因子：
5.2
作者：
Mastrangelo, Eloise;Pezzullo, Margherita;Milani, Mario
通讯作者：
Milani, Mario
影响因子：
30.3
作者：
Barrows NJ;Campos RK;Powell ST;Prasanth KR;Schott-Lerner G;Soto-Acosta R;Galarza-Muñoz G;McGrath EL;Urrabaz-Garza R;Gao J;Wu P;Menon R;Saade G;Fernandez-Salas I;Rossi SL;Vasilakis N;Routh A;Bradrick SS;Garcia-Blanco MA
通讯作者：
Garcia-Blanco MA
DOI：
10.1111/acer.13291
发表时间：
2017-03
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
MacLean RR;Valentine GW;Jatlow PI;Sofuoglu M
通讯作者：
Sofuoglu M
DOI：
10.4269/ajtmh.2005.73.122
发表时间：
2005-07-01
影响因子：
3.3
作者：
Pacanowski, J;Dos Santos, M;Cornet, M
通讯作者：
Cornet, M