The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats

Abstract This study investigated the impact of high-altitude hypoxic environment on the pharmacokinetics and respiratory effects of remimazolam in a rat model. Forty Sprague-Dawley rats were randomly divided into plain and plateau groups, with the plateau group exposed to a simulated altitude of 5,0...

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Bibliographic Details
Main Authors: Qingbin Chen, Li Deng, Zhen Jia
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-09447-4
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Summary:Abstract This study investigated the impact of high-altitude hypoxic environment on the pharmacokinetics and respiratory effects of remimazolam in a rat model. Forty Sprague-Dawley rats were randomly divided into plain and plateau groups, with the plateau group exposed to a simulated altitude of 5,000 m for 72 h prior to drug administration. Pharmacokinetic parameters, respiratory function, and safety profiles were evaluated following intravenous administration of remimazolam. Results showed that high-altitude exposure significantly altered remimazolam pharmacokinetics, with increased maximum plasma concentration (1368.2 ± 227.5 vs. 1025.6 ± 184.3 ng/mL), prolonged elimination half-life (63.5 ± 10.4 vs. 48.6 ± 8.2 min), and reduced clearance (0.89 ± 0.16 vs. 1.26 ± 0.24 L/h/kg) in the plateau group compared to the plain group. The plateau group also exhibited more pronounced respiratory depression, with greater decreases in PaO₂ and oxygen saturation, and higher incidence of adverse reactions. These findings suggest that high-altitude hypoxic environment significantly impacts remimazolam pharmacokinetics and respiratory effects, necessitating careful dose adjustment and monitoring in high-altitude clinical settings.
ISSN:2045-2322