THE PHARMACOKINETICS AND HEMODYNAMIC-EFFECTS OF INTRAVENOUS AND INTRAMUSCULAR DEXMEDETOMIDINE HYDROCHLORIDE IN ADULT HUMAN VOLUNTEERS
THE PHARMACOKINETICS AND HEMODYNAMIC-EFFECTS OF INTRAVENOUS AND INTRAMUSCULAR DEXMEDETOMIDINE HYDROCHLORIDE IN ADULT HUMAN VOLUNTEERS
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DOI：
10.1097/00000542-199305000-00002
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发表时间：
1993-05-01
期刊：
影响因子：
8.8
通讯作者：
SHAFER, SL
中科院分区：
文献类型：
--
作者：
DYCK, JB;MAZE, M;SHAFER, SL
背景右美托咪定是一种α 2受体激动剂，具有镇静和交感神经阻滞作用，在临床麻醉中具有潜在的应用价值。在单独的研究阶段中，通过静脉或肌内途径给予右美托咪定2 μ g/kg后，测定了10名健康男性志愿者的药代动力学和血流动力学变化。通过对观察到的浓度与从静脉内数据得出的单位分布函数进行去卷积，确定右美托咪定的肌内吸收曲线为双相。与静脉注射相同剂量相比，肌肉注射右美托咪定的生物利用度百分比为73 +/- 11%（平均值+/- SD）。肌内给药后，平均达峰时间为12 min（范围2-60 min），平均峰浓度为0.81 +/- 0.27 ng/ml。右美托咪定静脉给药后，血压出现双相变化。在5分钟静脉输注2 μ g/kg右美托咪定期间，平均动脉压（MAP）较基线值增加22%，心率（HR）较基线值下降27%。输注后4小时内，MAP较基线下降20%，HR上升至基线值以下5%。肌内给药后，血流动力学特征未显示急性变化。肌注后4 h内，MAP下降20%，HR下降10%。右美托咪定肌内给药避免了静脉给药观察到的急性血流动力学变化，但在4小时内导致相似的血流动力学变化。
Background. Dexmedetomidine is an alpha2 agonist with potential utility in clinical anesthesia for both its sedative and sympatholytic properties.Methods. The pharmacokinetics and hemodynamic changes that occurred in ten healthy male volunteers were determined after administration of dexmedetomidine 2 mug/kg by intravenous or intramuscular route in separate study sessions.Results. The intramuscular absorption profile of dexmedetomidine, as determined by deconvolution of the observed concentrations against the unit disposition function derived from the intravenous data, was biphasic. The percentage bio-availability of dexmedetomidine administered intramuscularly compared with the same dose administered intravenously was 73 +/- 11% (mean +/- SD). After intramuscular administration, the mean time to peak concentration was 12 min (range 2-60 min) and the mean peak concentration was 0.81 +/- 0.27 ng/ml. After intravenous administration of dexmedetomidine, there were biphasic changes in blood pressure. During the 5-min intravenous infusion of 2 mug/kg dexmedetomidine, the mean arterial pressure (MAP) increased by 22% and heart rate (HR) declined by 27% from baseline values. Over the 4 h after the infusion, MAP declined by 20% from baseline and HR rose to 5% below baseline values. The hemodynamic profile did not show acute alterations after intramuscular administration. During the 4 h after intramuscular administration, MAP declined by 20% and HR declined by 10%.Conclusions. The intramuscular administration of dexmedetomidine avoids the acute hemodynamic changes seen with intravenous administration, but results in similar hemodynamic alterations within 4 h.