Comparative study of the efficacy and pharmacokinetics of reduning injection and atomization inhalation

• Published in: Biomedicine & pharmacotherapy 2019-10, Vol.118, p.109226, Article 109226
• Main Authors: Zhang, Guangping, Li, Yingfei, Chen, Tengfei, Gao, Yunhang, Sun, Jing, Yang, Wei, Song, Ling, Su, Ping, Ma, Meng, Zhang, Zhongxiu, Zhang, Haijing, Yang, Yifei, Li, Han, Ye, Zuguang, Hou, Hongping
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Animals; Anti-Bacterial Agents - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Cough - drug therapy; Disease Models, Animal; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacokinetics; Drugs, Chinese Herbal - therapeutic use; Female; Injections; Leukocyte Count; Male; Nebulizers and Vaporizers; Pharmacodynamics; Pharmacokinetics; Pneumonia - blood; Pneumonia - drug therapy; Pneumonia - pathology; Protective Agents - pharmacology; Protective Agents - therapeutic use; Rats, Sprague-Dawley; Rats, Wistar; Reduning inhalation solution; Reduning injection; Temperature; Tissue Distribution; Treatment Outcome
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2019.109226

The effects of Reduning injection and nebulized inhalation for treating upper respiratory tract infections were compared, including anti-bacterial, anti-viral, anti-inflammatory, anti-pyretic, anti-tussive, and anti-phlegm. Using chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, and geniposide as the index components, the pharmacokinetics and tissue distributions were compared. Influenza virus PR8-infected mice in the Reduning groups showed significantly reduced mortality and prolonged survival time. The white blood cell count was significantly reduced in the 20- and 10-min groups. Inhalation significantly decreased the temperature from 2 h in the 20- and 10-min groups. Inhalation significantly reduced the cough rate but not cough latency. Phenol red excretion was significantly increased in all Reduning groups. The elimination half-life of geniposide after inhalation in male and female rats was 2.05–5.28 and 4.03–10.4 h, respectively, which was much greater than after injection. Regarding tissue distribution, the injection dose (2 mL/kg) was 50 times the inhalation dose, and maximum serum concentration (Cmax) and AUCINF_obs of the four components in the trachea and lung were 0.95–11.1 and 0.59–4.36 times the inhalation values, respectively. Plasma Cmax and AUCINF_obs were 160–637 and 22.7–180 times the inhalation values, respectively. Atomized Reduning dose was equivalent to 1/90 of the mouse injection dose, and the effects of inhalation were similar or superior to those of injections. Atomization inhalation is targeted to the lungs, so systemic drug exposure was greatly reduced and lung concentration was high, which may increase the efficacy and reduce the safety risks associated with injections.