Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine.
Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine.
复制标题
DOI：
10.1007/s40262-017-0507-7
复制
发表时间：
2017-08
影响因子：
4.5
通讯作者：
Colin P
中科院分区：
文献类型：
--
作者：
Weerink MAS;Struys MMRF;Hannivoort LN;Barends CRM;Absalom AR;Colin P
右美托咪定是一种α-2肾上腺素能受体激动剂，具有镇静、抗焦虑、解交感和止痛作用，对呼吸功能的抑制作用最小。它对α2受体有很强的选择性，α2：α1的比率为1620：1。血液动力学效应，包括一过性高血压、心动过缓和低血压，是由药物的外周血管收缩和交感神经特性引起的。右美托咪定通过激活蓝斑突触前和突触后的α2受体发挥催眠作用，从而诱导一种类似自然睡眠的无意识状态，独特的方面是患者保持容易唤醒和合作。右美托咪定分布迅速，主要通过葡萄糖醛酸化和羟化作用在肝脏代谢成非活性代谢物。右美托咪定药代动力学的个体间变异性很高，特别是在重症监护病房人群中。近年来，进行了多药动学、非房室分析和群体药代动力学研究。身体大小、肝脏损害以及可能的血浆白蛋白和心输出量对右美托咪定的药代动力学有重大影响。关于其他协变量的结果仍然没有定论，值得进一步研究。虽然最初只被批准在成人重症监护病房人群中静脉注射使用长达24小时，但在过去几年中，右美托咪定在临床实践中的应用范围已经扩大。2003年，美国食品和药物管理局还批准了右旋美托咪定的程序性镇静，右旋美托咪定已被用于多种非标签应用，如儿童镇静、鼻腔或口腔给药，并用作局部止痛技术的辅助。
Dexmedetomidine is an α2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for α2-receptors with an α2:α1 ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug’s peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic α2-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative. Dexmedetomidine is rapidly distributed and is mainly hepatically metabolized into inactive metabolites by glucuronidation and hydroxylation. A high inter-individual variability in dexmedetomidine pharmacokinetics has been described, especially in the intensive care unit population. In recent years, multiple pharmacokinetic non-compartmental analyses as well as population pharmacokinetic studies have been performed. Body size, hepatic impairment, and presumably plasma albumin and cardiac output have a significant impact on dexmedetomidine pharmacokinetics. Results regarding other covariates remain inconclusive and warrant further research. Although initially approved for intravenous use for up to 24 h in the adult intensive care unit population only, applications of dexmedetomidine in clinical practice have been widened over the past few years. Procedural sedation with dexmedetomidine was additionally approved by the US Food and Drug Administration in 2003 and dexmedetomidine has appeared useful in multiple off-label applications such as pediatric sedation, intranasal or buccal administration, and use as an adjuvant to local analgesia techniques.
登录
查看更多内容
影响因子：
8.8
作者：
DOZE, VA;CHEN, BX;MAZE, M
通讯作者：
MAZE, M
影响因子：
8.8
作者：
Blaudszun, Gregoire;Lysakowski, Christopher;Tramer, Martin R.
通讯作者：
Tramer, Martin R.
影响因子：
2.1
作者：
AANTAA, R;KANTO, J;SCHEININ, M
通讯作者：
SCHEININ, M
影响因子：
3.2
作者：
Dholakia, Chirag;Beverstein, Gretchen;Gould, Jon C.
通讯作者：
Gould, Jon C.
影响因子：
8.8
作者：
Angst, MS;Ramaswamy, B;Maze, M
通讯作者：
Maze, M