Veterinary anaesthesia and analgesia · 2024
Pharmacokinetics of methadone after intravenous and subcutaneous administration in domestic ferrets (Mustela putorius furo).
СтатьяClinical Trial, VeterinaryНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shin Chi Won, Knych Heather, Desprez Isabelle, Ambros Barbara
Аннотация
OBJECTIVE: To determine the pharmacokinetic profile of methadone after intravenous (IV) and subcutaneous (SC) administration in domestic ferrets (Mustela putorius furo).
STUDY DESIGN: Crossover experimental study.
ANIMALS: A group of eight healthy adult ferrets weighing 1.01 ± 0.23 kg (mean ± standard deviation).
METHODS: Methadone hydrochloride (0.3 mg kg-1) was injected IV or SC to each ferret with a 3 week washout period. Blood samples were collected via a jugular catheter before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360 and 480 minutes after drug administration. Liquid chromatography-tandem mass spectrometry was used to determine plasma methadone concentrations. A nonlinear mixed effects model was used to analyze the data.
RESULTS: After IV injection, systemic clearance (Clss) and volume of distribution (Vdss) were 78.9 mL min-1 kg-1 and 9.8 L kg-1, respectively. Elimination half-life was 2.0 hours and SC bioavailability was fixed at 1. The maximum observed plasma concentration after SC injection was 92.1 ± 76.8 ng mL-1. Behavioral changes were observed after both routes.
CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetic profile of IV methadone was characterized by a high Clss and large Vdss, with high bioavailability and absorption rate after SC administration. Half-life was short and mean plasma methadone concentrations stayed above the minimum effective concentration (MEC) reported in humans only after SC administration for 5 minutes, but remained above that reported in dogs for 45 minutes following both routes. Further studies investigating the MEC and pharmacodynamics of methadone in ferrets are warranted.
STUDY DESIGN: Crossover experimental study.
ANIMALS: A group of eight healthy adult ferrets weighing 1.01 ± 0.23 kg (mean ± standard deviation).
METHODS: Methadone hydrochloride (0.3 mg kg-1) was injected IV or SC to each ferret with a 3 week washout period. Blood samples were collected via a jugular catheter before and 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360 and 480 minutes after drug administration. Liquid chromatography-tandem mass spectrometry was used to determine plasma methadone concentrations. A nonlinear mixed effects model was used to analyze the data.
RESULTS: After IV injection, systemic clearance (Clss) and volume of distribution (Vdss) were 78.9 mL min-1 kg-1 and 9.8 L kg-1, respectively. Elimination half-life was 2.0 hours and SC bioavailability was fixed at 1. The maximum observed plasma concentration after SC injection was 92.1 ± 76.8 ng mL-1. Behavioral changes were observed after both routes.
CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetic profile of IV methadone was characterized by a high Clss and large Vdss, with high bioavailability and absorption rate after SC administration. Half-life was short and mean plasma methadone concentrations stayed above the minimum effective concentration (MEC) reported in humans only after SC administration for 5 minutes, but remained above that reported in dogs for 45 minutes following both routes. Further studies investigating the MEC and pharmacodynamics of methadone in ferrets are warranted.