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Peterbauer C Larenza PM Knobloch M Theurillat R Thormann W Mevissen M Spadavecchia C 《Veterinary anaesthesia and analgesia》2008,35(5):414-423
ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies.Study designProspective, blinded, cross-over study.AnimalsSix healthy 5-year-old Shetland ponies.MethodsPonies received either 0.6 mg kg−1 racemic ketamine (group RS) or 0.3 mg kg−1 S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg−1minute−1 racemic ketamine (group RS) or 10 μg kg−1minute−1 S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate.ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL−1 of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL−1) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups.ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary. 相似文献
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《Veterinary anaesthesia and analgesia》2020,47(2):168-176
ObjectiveTo assess the differences in the pharmacokinetic profiles of S-ketamine, R-ketamine and their metabolites, S-norketamine and R-norketamine, and to measure relevant physiologic variables after intravenous administration of racemic (RS) ketamine or S-ketamine alone in Beagle dogs sedated with medetomidine.Study designExperimental, blinded and randomized crossover study.AnimalsA total of six (three female and three male) adult Beagle dogs.MethodsMedetomidine (450 μg m–2) was administered intramuscularly, followed by either S-ketamine (2 mg kg–1) or RS-ketamine (4 mg kg–1) 20 minutes later, both administered intravenously. Blood samples were collected before medetomidine administration and at multiple time points 1–900 minutes following the ketamine administration. Plasma samples were analysed using liquid chromatography–tandem mass spectrometry. Heart rate, respiratory rate, noninvasive blood pressure, haemoglobin saturation with oxygen and body temperature were measured at baseline, before ketamine administration, and 1, 2, 5, 10, 15, 20 and 30 minutes after ketamine administration. All cardiovascular variables, blood glucose, haemoglobin and lactate concentrations were analysed using different linear mixed effects models; the significance was set at p < 0.05.ResultsS-ketamine showed a two-compartment kinetic profile; no statistically significant differences were observed between its concentrations or in the calculated pharmacokinetic parameters following S- or RS-ketamine. When the racemic mixture was administered, no differences were detected between R- and S-ketamine concentrations, but the area under the curve (AUC) for R-norketamine was significantly lower than that for S-norketamine. Clinically relevant physiologic variables did not show statistically significant differences following the administration of the racemic mixture or of S-ketamine alone.Conclusions and clinical relevanceThis study performed in dogs showed that RS-ketamine and S-ketamine combined with medetomidine showed enantioselective pharmacokinetics as S- and R-norketamine AUCs were different, but S-ketamine levels were identical. 相似文献
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Daniela Casoni Claudia Spadavecchia Beat Wampfler Wolfgang Thormann Olivier L Levionnois 《Acta veterinaria Scandinavica》2015,57(1)
Background
Intravenous anaesthetic drugs are the primary means for producing general anaesthesia in equine practice. The ideal drug for intravenous anaesthesia has high reliability and pharmacokinetic properties indicating short elimination and lack of accumulation when administered for prolonged periods. Induction of general anaesthesia with racemic ketamine preceded by profound sedation has already an established place in the equine field anaesthesia. Due to potential advantages over racemic ketamine, S-ketamine has been employed in horses to induce general anaesthesia, but its optimal dose remains under investigation. The objective of this study was to evaluate whether 2.5 mg/kg S-ketamine could be used as a single intravenous bolus to provide short-term surgical anaesthesia in colts undergoing surgical castration, and to report its pharmacokinetic profile.Results
After premedication with romifidine and L-methadone, the combination of S-ketamine and diazepam allowed reaching surgical anaesthesia in the 28 colts. Induction of anaesthesia as well as recovery were good to excellent in the majority (n = 22 and 24, respectively) of the colts. Seven horses required additional administration of S-ketamine to prolong the duration of surgical anaesthesia. Redosing did not compromise recovery quality. Plasma concentration of S-ketamine decreased rapidly after administration, following a two-compartmental model, leading to the hypothesis of a consistent unchanged elimination of the parent compound into the urine beside its conversion to S-norketamine. The observed plasma concentrations of S-ketamine at the time of first movement were various and did not support the definition of a clear cut-off value to predict the termination of the drug effect.Conclusions
The administration of 2.5 mg/kg IV S-ketamine after adequate premedication provided good quality of induction and recovery and a duration of action similar to what has been reported for racemic ketamine at the dose of 2.2 mg/kg. Until further investigations will be provided, close monitoring to adapt drug delivery is mandatory, particularly once the first 10 minutes after injection are elapsed. Taking into account rapid elimination of S-ketamine, significant inter-individual variability and rapid loss of effect over a narrow range of concentrations a sudden return of consciousness has to be foreseen. 相似文献
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