中国药理学与毒理学杂志2025，Vol.39Issue(6)：419-424,6.DOI:10.3867/j.issn.1000-3002.2025.08368
右美托咪定在比格犬不同黏膜给药部位的药动学及镇静效果研究
Sedation effects and pharmacokinetics of dexmedetomidine at different sites of mucosal administration in beagle dogs
摘要
Abstract
OBJECTIVE To establish an ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of dexmedetomidine(DEX)in plasma of beagle dogs and evaluate the pharmacokinetics and sedation after nasal,buccal and sublingual mucosal admin-istration.METHODS A UPLC-MS/MS method was established and validated for dertermination of DEX in plasma of beagle dogs.DEX was administered to the nasal cavity,buccal and sublingual mucous membranes of beagle dogs,respectively.Blood samples were collected at different time points.The plasma concentration of DEX was measured by the established UPLC-MS/MS method.Pharmacokinetic parameters were fitted by Phoenix software and the sedative effect at different mucous membrane sites was evaluated in conjunction with behavioral and Ramsay scores.RESULTS The linearity of DEX was fine within the range of 0.05-100 μg·L-1(r>0.999),which was validated methodologically to meet the requirements of quantitative detection.The plasma concentration of the drug peaked the fastest with nasal administration.Tmax was 0.25 h,Cmax(4.43±1.19)μg·L-1,and the AUC0-6h was(8.92±2.07)μg·h·L-1,compared with 0.92 and 1 h,(2.87±0.69),(2.70±0.41)μg·L-1,and(7.99±1.77),(7.01±2.09)μg·h·L-1 with buccal and sublingual administration.Nasal administration had the fastest onset at 7 min,with a Ramsay score of 4,and sedation lasted for 36 min,compared with 33 and 35 min,and 38 and 37 min for buccal and sublingual administration.CONCLUSION The proposed method is sensitive,reliable and applicable to quantitative analysis of DEX in plasma of beagle dogs.Administration of DEX to the nasal cavity mucosa has a faster onset and a better sedative effect than to the buccal and sublingual mucosa.关键词
右美托咪定/黏膜给药/超高效液相色谱-串联质谱/药代动力学/镇静Key words
dexmedetomidine/mucosal administration/ultra performance liquid chromatography-tandem mass spectrometry/pharmacokinetics/sedation分类
医药卫生引用本文复制引用
王盛源,李先福,刘圆圆,赵子明,王增明,郑爱萍..右美托咪定在比格犬不同黏膜给药部位的药动学及镇静效果研究[J].中国药理学与毒理学杂志,2025,39(6):419-424,6.基金项目
国家重点研发计划(2023YFC2706100) National Key Research and Development Program(2023YFC2706100) （2023YFC2706100）
