Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies

Gittel, Claudia; Schulz‐Kornas, Ellen; Sandbaumhüter, Friederike Andrea; Theurillat, Regula; Vervuert, Ingrid; Menzies, M. Paula Larenza; Thormann, Wolfgang; Braun, Christina

doi:10.1016/j.vaa.2020.04.018

Cited by 2 publications

(3 citation statements)

References 37 publications

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“…It is important to mention that it represents the first enantioselective study of the methadone to EDDP metabolic step in equines. The methadone assay was also used to investigate the pharmacokinetics of l ‐methadone and l ‐EDDP after administration of a commercially available combination of l ‐methadone with fenpipramide to isoflurane anesthetized ponies [97]. Similarly, the assays for chlorpheniramine and brompheniramine were found to be applicable to stereoselective pharmacokinetic investigations of their enantiomers in the rat [54,55].…”

Section: Applicationsmentioning

confidence: 99%

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

Caslavska

Thormann

2021

Electrophoresis

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The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis‐ based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field‐amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.

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Section: Applicationsmentioning

confidence: 99%

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

Caslavska

Thormann

2021

Electrophoresis

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“…These parameters bear a resemblance to those reported for racemic methadone after the IV administration of a single bolus of 0.15 mg/mL to unpremedicated horses [ 13 ]. The pharmacokinetics of l ‐methadone in the current study look alike to those obtained after equivalent dose administration (i.e., bolus of 0.25 mg/kg IV) of a proprietary formulation of l ‐methadone and fenpipramide (i.e., l ‐Polamivet ®) to anesthetized Shetland ponies that were sedated and premedicated differently [ 23 ]. In the case of the CRI trial, there was insufficient data for a pharmacokinetic analysis.…”

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confidence: 93%

“…The latter assay was successfully applied to elucidate the pharmacokinetics of ketamine in Beagle dogs [ 22 ]. The assay for methadone and EDDP was employed in a study with bolus IV application of a combination of l ‐methadone and fenpipramide to anesthetized Shetland ponies that were sedated with detomidine and butorphanol and premedicated with detomidine [ 23 ]. In this article, we now report its use to determine the enantiomer levels in arterial plasma samples that were collected in a pharmacokinetic study after application of racemic methadone to Shetland ponies that were sedated and premedicated with romifidine.…”

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confidence: 99%

Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis

et al. 2021

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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-1,5dimethyl-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. dmethadone 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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Pharmacokinetics and pharmacodynamics of l-methadone in isoflurane-anaesthetized and mechanically ventilated ponies

Cited by 2 publications

References 37 publications

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

Stereoselective methadone disposition after administration of racemic methadone to anesthetized Shetland ponies assessed by capillary electrophoresis

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