AUTHOR=Liu Fengying , Sui Xin , Wang Qian , Li Jinglai , Yang Weijie , Yang Yi , Xiao Zhenyu , Sun Yangyang , Guo Xiaoxuan , Yang Xinyi , Yang Jun , Wang Yongan , Luo Yuan 

TITLE=Insights into the pharmacodynamics and pharmacokinetics of meldonium after exposure to acute high altitude

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1119046

DOI=10.3389/fphar.2023.1119046

ISSN=1663-9812

ABSTRACT=Meldonium, as a well-known cardioprotective drug, has been reported to be protective against pulmonary injury at high altitudes; however, the pharmacodynamics of meldonium in other vital organs under acute high-altitude injury are less investigated and the related pharmacokinetics have not been fully elucidated. The present study examined the basic pharmacodynamics and pharmacokinetics (PK) in rat exposure to acute high-altitude hypoxia after oral and intravenous pre-administration of meldonium. The results indicate that meldonium can improve acute hypoxia-induced pathological damage in brain and lung tissues, and restore blood biochemistry and routine blood index of heart, liver and kidney tissues under a simulated acute high-altitude environment. Furthermore, compared to the normoxia group, rats exposed to simulated high-altitude hypoxia and premedicated with oral meldonium showed linear kinetics in the dose range of 25-100 mg/kg, with significantly increase in the area under curve (AUC) and half-life and reduced clearance rate. No significant differences in these meldonium PK parameters of were observed with intravenous administration. Additionally, meldonium was involved in the regulation of succinic acid and 3-hydroxypropionic acid. These results will contribute to our understanding of the preclinical PK properties of meldonium and its acute high-altitude protective effects.