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...

Full description

Saved in:
Bibliographic Details
Main Authors: Qingbin Chen, Li Deng, Zhen Jia
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-09447-4
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849763891800702976
author Qingbin Chen
Li Deng
Zhen Jia
author_facet Qingbin Chen
Li Deng
Zhen Jia
author_sort Qingbin Chen
collection DOAJ
description 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.
format Article
id doaj-art-76984dfcd0164d1eb7fd59263aae3c80
institution DOAJ
issn 2045-2322
language English
publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-76984dfcd0164d1eb7fd59263aae3c802025-08-20T03:05:17ZengNature PortfolioScientific Reports2045-23222025-07-011511810.1038/s41598-025-09447-4The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in ratsQingbin Chen0Li Deng1Zhen Jia2Department of Surgical Anesthesiology, Affiliated Hospital of Qinghai UniversityDepartment of Surgical Anesthesiology, Affiliated Hospital of Qinghai UniversityDepartment of Surgical Anesthesiology, Affiliated Hospital of Qinghai UniversityAbstract 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.https://doi.org/10.1038/s41598-025-09447-4RemimazolamHigh-altitude hypoxiaPharmacokineticsRespiratory functionDrug metabolismSedation
spellingShingle Qingbin Chen
Li Deng
Zhen Jia
The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats
Scientific Reports
Remimazolam
High-altitude hypoxia
Pharmacokinetics
Respiratory function
Drug metabolism
Sedation
title The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats
title_full The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats
title_fullStr The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats
title_full_unstemmed The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats
title_short The effects of high-altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam: an experimental study in rats
title_sort effects of high altitude hypoxic environment on the pharmacokinetics and respiratory function of remimazolam an experimental study in rats
topic Remimazolam
High-altitude hypoxia
Pharmacokinetics
Respiratory function
Drug metabolism
Sedation
url https://doi.org/10.1038/s41598-025-09447-4
work_keys_str_mv AT qingbinchen theeffectsofhighaltitudehypoxicenvironmentonthepharmacokineticsandrespiratoryfunctionofremimazolamanexperimentalstudyinrats
AT lideng theeffectsofhighaltitudehypoxicenvironmentonthepharmacokineticsandrespiratoryfunctionofremimazolamanexperimentalstudyinrats
AT zhenjia theeffectsofhighaltitudehypoxicenvironmentonthepharmacokineticsandrespiratoryfunctionofremimazolamanexperimentalstudyinrats
AT qingbinchen effectsofhighaltitudehypoxicenvironmentonthepharmacokineticsandrespiratoryfunctionofremimazolamanexperimentalstudyinrats
AT lideng effectsofhighaltitudehypoxicenvironmentonthepharmacokineticsandrespiratoryfunctionofremimazolamanexperimentalstudyinrats
AT zhenjia effectsofhighaltitudehypoxicenvironmentonthepharmacokineticsandrespiratoryfunctionofremimazolamanexperimentalstudyinrats