Analysis of the ketamine binding to total plasma protein from domestic cats

Victória Paradela Pereira  Motta; Fernanda Ferreira da  Silva; Ícaro Putinhon  Caruso; Paulo Roberto Nunes de  Goes; Marilda Onghero  Taffarel; Andrea  Diniz; Flavio Augusto Vicente Seixas

doi:10.11606/issn.1678-4456.bjvras.2024.219363

Authors

Victória Paradela Pereira Motta Universidade Estadual de Maringá, Departamento de Medicina Veterinária
Fernanda Ferreira da Silva Universidade Estadual de Maringá, Departamento de Medicina Veterinária
Ícaro Putinhon Caruso Universidade Estadual Paulista “Júlio de Mesquita Filho”, Departamento de Física https://orcid.org/0000-0003-4464-0520
Paulo Roberto Nunes de Goes Universidade Estadual de Maringá, Departamento de Farmácia https://orcid.org/0000-0001-7220-0739
Marilda Onghero Taffarel Universidade Estadual de Maringá, Departamento de Medicina Veterinária https://orcid.org/0000-0002-6643-3461
Andrea Diniz Universidade Estadual de Maringá, Departamento de Farmácia https://orcid.org/0000-0002-9638-9246
Flavio Augusto Vicente Seixas Universidade Estadual de Maringá, Departamento de Tecnologia https://orcid.org/0000-0002-0117-6919

DOI:

https://doi.org/10.11606/issn.1678-4456.bjvras.2024.219363

Keywords:

Drug development, Analgesia, Felis catus, Albumin

Abstract

Ketamine is a versatile veterinary, clinical, and hospital drug. Evaluating the binding parameters of ketamine to total plasma proteins from domestic cats provides necessary information in determining the value of the pharmacokinetic parameter named distribution volume, which is used for the consequent prospection of drug concentrations in clinical trials. This work aimed to evaluate the binding rate of ketamine to total plasma proteins, the binding constant, and the binding mode to serum albumin in cats. After approval of the project by CEUA/UEM (protocol 3292020621), a plasma pool from six animals (n=6) was reinforced with ketamine concentrations aiming for ultrafiltration with a 10 kDa cutoff membrane device. The drug levels before and after ultrafiltration were analyzed using the liquid chromatography-mass spectrometry technique (LC- MS/MS). The results were calculated using a Scatchard plot to calculate the binding rate and binding constant to albumin. Docking simulations identified the most likely albumin-binding sites. The ketamine binding rate was 65% when the drug reached a plasma concentration above 300 ng⋅mL-1, and the binding constant (Kb) was 2×106 mol⋅L–1 with a positive Hill coefficient (nH) of 2.3. These results show a good correlation between the physicochemical parameters of the drug with structural evaluation by docking simulations and coherence with the values reported by other methodologies in recent literature. This work brought data on the ketamine-binding behavior in cats, an important parameter for future pharmacokinetic evaluations in the search for better protocols for the clinical use of this drug in veterinary medicine.

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Analysis of the ketamine binding to total plasma protein from domestic cats

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