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document
Clinical pharmacology of methadone in dogs . OBJECTIVE To investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs . STUDY DESIGN Randomized , cross-over , experimental trial . ANIMALS Nine adult dogs ( beagle and beagle cross breeds ) , four males and five females . METHODS Methadone hydrochloride , 0.4 mg kg ( -1 ) , was administered intravenously ( IV ) and subcutaneously ( SC ) with a crossover design . Drug and hormone analyses in plasma were performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and radioimmunoassay respectively . Behavioural data were collected using a standardized protocol . RESULTS After IV administration , the plasma concentration of methadone at 10 minutes was 82.1 +/- 9.2 ng mL ( -1 ) ( mean +/- SD ) , the terminal half-life was 3.9 +/- 1.0 hours , the volume of distribution 9.2 +/- 3.3 L kg ( -1 ) and plasma clearance 27.9 +/- 7.6 mL minute ( -1 ) kg ( -1 ) . After SC administration , time to maximal plasma concentration was 1.26 +/- 1.04 hours and maximal plasma concentration of methadone was 23.9 +/- 14.4 ng mL ( -1 ) , the terminal half-life was 10.7 +/- 4.3 hours and bioavailability was 79 +/- 22 % . Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone . The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration . The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic . CONCLUSION AND CLINICAL RELEVANCE When methadone was administered by the SC route , the half-life was longer , but the individual variation in plasma concentrations was greater compared with IV administration . Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain . Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment .
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
Methadone hydrochloride
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Intervention_Physical
Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry
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Intervention_Physical
radioimmunoassay
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Intervention_Pharmacological
methadone
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Outcome_Physical
pharmacokinetics
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Outcome_Mental
behaviour
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Outcome_Physical
plasma concentrations of cortisol and vasopressin
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Outcome_Mental
Behavioural data
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Outcome_Physical
plasma concentration of methadone
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Outcome_Physical
Concentrations of both cortisol and vasopressin
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Outcome_Mental
licking and swallowing
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Outcome_Mental
whining
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Outcome_Pain
pain
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Outcome_Physical
variation in plasma concentrations
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Outcome_Mental
frequency of whining
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Outcome_Mental
Cortisol and vasopressin concentrations in plasma
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Outcome_Pain
analgesia
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Participant_Condition
dogs .
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Participant_Condition
healthy dogs .
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Participant_Condition
Nine adult dogs ( beagle and beagle cross breeds ) , four males and five females .