Pharmacokinetics of combinations of dexmedetomidine, vatinoxan and ketamine in male neutered cats.

IF 1.4 2区农林科学 Q2 VETERINARY SCIENCES

Veterinary anaesthesia and analgesia Pub Date : 2025-01-30 DOI:10.1016/j.vaa.2025.01.015

Bruno H Pypendop, Yu Hong Law, Juhana Honkavaara, Linda S Barter

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引用次数: 0

Abstract

Objective: To characterize the pharmacokinetics of combinations of dexmedetomidine, vatinoxan and ketamine in cats.

Study design: Partially randomized, crossover, experimental study.

Animals: A group of six healthy male neutered cats, aged 1-2 years, weighing 5.4 ± 0.3 kg.

Methods: Each cat was administered six treatments: dexmedetomidine (25 μg kg^-1; D) + vatinoxan (600 μg kg^-1; V) + ketamine (2.5 mg kg^-1; K2.5) intramuscularly (IM) (DVK2.5IM); D + V + ketamine (5 mg kg^-1; K5) IM (DVK5IM); D + V + ketamine (10 mg kg^-1; K10) IM (DVK10IM); D + K5 IM (DK5IM); D + V + K5 subcutaneously (SC) (DVK5SC); or D + V + K5 intravenously (IV) (DVK5IV). Venous blood samples were collected before treatment injection, and at various times up to 6 hours thereafter. Plasma dexmedetomidine, vatinoxan and ketamine concentrations were measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-plasma dexmedetomidine, vatinoxan and ketamine data using nonlinear mixed effect modeling, including covariates for the effects of vatinoxan and the dose of ketamine where appropriate.

Results: Two-compartment models best fitted the time-plasma dexmedetomidine, vatinoxan and ketamine concentrations. The models predicted that vatinoxan increases the clearance of dexmedetomidine and decreases the bioavailability of IM ketamine and that increasing doses of ketamine increase the volume of the central compartment for dexmedetomidine and the bioavailability of IM ketamine. The volume of distribution at steady state (mL kg^-1) and metabolic clearance (mL minute^-1 kg^-1) were 1012-2429 and 12.5-15.4 for dexmedetomidine, 666 and 3.7 for vatinoxan and 2260 and 23.8 for ketamine, respectively. Bioavailability (%) for IM and SC dexmedetomidine, vatinoxan and ketamine was 83 and 95, 99 and 95 and 60-100 and 100, respectively.

Conclusions and clinical relevance: The pharmacokinetics of dexmedetomidine and the bioavailability of ketamine were affected by vatinoxan and the dose of ketamine.

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来源期刊

Veterinary anaesthesia and analgesia 农林科学-兽医学

CiteScore

3.10

自引率

17.60%

发文量

审稿时长

97 days

期刊介绍： Veterinary Anaesthesia and Analgesia is the official journal of the Association of Veterinary Anaesthetists, the American College of Veterinary Anesthesia and Analgesia and the European College of Veterinary Anaesthesia and Analgesia. Its purpose is the publication of original, peer reviewed articles covering all branches of anaesthesia and the relief of pain in animals. Articles concerned with the following subjects related to anaesthesia and analgesia are also welcome: the basic sciences; pathophysiology of disease as it relates to anaesthetic management equipment intensive care chemical restraint of animals including laboratory animals, wildlife and exotic animals welfare issues associated with pain and distress education in veterinary anaesthesia and analgesia. Review articles, special articles, and historical notes will also be published, along with editorials, case reports in the form of letters to the editor, and book reviews. There is also an active correspondence section.