Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis.
Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis.
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用毛细管电泳法评价了外消旋美沙酮对麻醉设得兰矮种马的立体选择性处置。
DOI：
10.1002/elps.202100115
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发表时间：
2021-09
期刊：
影响因子：
2.9
通讯作者：
Braun C
中科院分区：
文献类型：
--
作者：
Sandbaumhüter FA;Gittel C;Larenza-Menzies MP;Theurillat R;Thormann W;Braun C
在麻醉的设得兰群岛小马中，研究了单次静脉内（0.5 mg/kg盐酸美沙酮; n = 6）或恒速输注（0.25 mg/kg推注，然后是0.25 mg/kg/h盐酸美沙酮; n = 3）给予外消旋美沙酮后美沙酮药代动力学的对映体选择性。分别通过CE（使用高度硫酸化γ-环糊精作为手性选择剂）和电动分析物进样（从碱性pH条件下制备的液/液浸提液中）分析了l-美沙酮和d-美沙酮及其主要代谢产物l-和d-2-亚乙基-1，5-二甲基-3，3-二苯基吡咯烷（EDDP）的血浆浓度。在两项试验中，d-美沙酮浓度低于l-美沙酮，d-EDDP水平低于L-EDDP。对于单次静脉推注的情况，采用二室药代动力学模型分析美沙酮对映体的血浆浓度-时间曲线。与d-美沙酮相比，l-美沙酮的消除速率常数较慢，体内清除率较低，稳态分布容积较小。d-美沙酮和d-EDDP的消除速度快于其各自的L-对映体。这是第一个研究，概述了处置外消旋美沙酮给药麻醉马是对映体选择性。
The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l‐methadone and d‐methadone and their major metabolites, l‐ and d‐2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ‐cyclodextrin as chiral selector and electrokinetic analyte injection from liquid/liquid extracts prepared at alkaline pH. In both trials, the d‐methadone concentrations were lower than those of l‐methadone and the d‐EDDP levels were lower than those of L‐EDDP. For the case of a single intravenous bolus injection, the plasma concentration versus time profile of methadone enantiomers was analyzed with a two‐compartment pharmacokinetic model. l‐methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady‐state volume of distribution than d‐methadone. d‐methadone and d‐EDDP were eliminated faster than their respective l‐enantiomers. This is the first study that outlines that the disposition of racemic methadone administered to anesthetized equines is enantioselective.
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