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Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis
Author(s) -
Sandbaumhüter Friederike A.,
Gittel Claudia,
LarenzaMenzies M. Paula,
Theurillat Regula,
Thormann Wolfgang,
Braun Christina
Publication year - 2021
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.202100115
Subject(s) - methadone , chemistry , pharmacokinetics , enantiomer , intravenous bolus , pharmacology , volume of distribution , anesthesia , chromatography , medicine , stereochemistry
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.