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<p>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&#xa0;m for 72&#xa0;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&#xa0;min), and reduced clearance (0.89 ± 0.16 vs. 1.26 ± 0.24&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月8日

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  • Qingbin Chen,
  • Li Deng,
  • Zhen Jia

摘要

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.