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Antinociceptive effects and farmacokinetics in horses treated with different low doses of methadone and detomidine

Grant number: 14/00474-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2015
Effective date (End): May 31, 2018
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Stelio Pacca Loureiro Luna
Grantee:Miguel Gozalo Marcilla
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated research grant:10/08967-0 - Evaluation of clinical and experimental pain in animals, AP.TEM
Associated scholarship(s):17/01425-6 - Clinical application of different constant rate infusions of detomidine and methadone in standing horses, BE.EP.PD

Abstract

Pain interferes with different organic functions and its prevention and treatment is very important in veterinary medicine. The use of intravenous (IV) opioids in the equine has limitations, mainly due to their adverse effects. Methadone is a µ synthetic agonist, with similar properties as morphine, being also antagonist at the N-methyl-D aspartate (NMDA) receptors. Although its farmacokinetics have been reported in horses, the use of methadone may cause hyperesthesia and ataxia when used alone. Alpha-2-agonists such as detomidine, produce analgesia whereas producing cardiorespiratory depression. The hypothesis of this project is that the association of low doses of detomidine with normal doses of methadone will produce analgesia and small adverse effects. In this context, it will be determined the lower doses of detomidine that would allow the clinical use of methadone. In order to do that, eight adult horses will receive five IV treatments randomly: CONTROL (saline), M (methadone), MDB (methadone with low dose of detomidine), MDM (methadone with medium dose) and MDA (methadone with high dose), with a washout period of one week. The antinociceptive activity will be evaluated by the use of electrical, temperature and pressure stimuli. Heart and respiratory frequencies, sedation levels, gastrointestinal motility, non invasive blood pressure, farmacokinetics and farmacodynamics will be measured. With this project it is expected to determine the minimal doses of alpha-2-agonists in combination with normal doses of methadone that will produce antinociception, with no adverse effects and minimal degree of sedation. In a further phase of the project, and according with the results obtained, the use of constant rate infusions of different combinations of detomidine and methadone will be studied.

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GOZALO-MARCILLA, M.; DE OLIVEIRA, A. R.; FONSECA, M. W.; POSSEBON, F. S.; PELLIGAND, L.; TAYLOR, P. M.; LUNA, S. P. L. Sedative and antinociceptive effects of different detomidine constant rate infusions, with or without methadone in standing horses. EQUINE VETERINARY JOURNAL, v. 51, n. 4, p. 530-536, JUL 2019. Web of Science Citations: 2.
GOZALO-MARCILLA, M.; LUNA, S. P. L.; MOREIRA DA SILVA, R.; CROSIGNANI, N.; LOPES, N. P.; TAYLOR, P. M.; PELLIGAND, L. Characterisation of the in vivo interactions between detomidine and methadone in horses: Pharmacokinetic and pharmacodynamic modelling. EQUINE VETERINARY JOURNAL, v. 51, n. 4, p. 517-529, JUL 2019. Web of Science Citations: 1.
GOZALO-MARCILLA, MIGUEL; LUNA, STELIO P. L.; GASTHUYS, FRANK; POLLARIS, ELKE; VLAMINCK, LIEVEN; MARTENS, ANN; HASPESLAGH, MAARTEN; SCHAUVLIEGE, STIJN. Clinical applicability of detomidine and methadone constant rate infusions for surgery in standing horses. VETERINARY ANAESTHESIA AND ANALGESIA, v. 46, n. 3, p. 325-334, MAY 2019. Web of Science Citations: 0.
SCHAUVLIEGE, STIJN; CUYPERS, CHARLOTTE; MICHIELSEN, ANNELEEN; GASTHUYS, FRANK; GOZALO-MARCILLA, MIGUEL. How to score sedation and adjust the administration rate of sedatives in horses: a literature review and introduction of the Ghent Sedation Algorithm. VETERINARY ANAESTHESIA AND ANALGESIA, v. 46, n. 1, p. 4-13, JAN 2019. Web of Science Citations: 1.
GOZALO-MARCILLA, M.; GASTHUYS, F.; LUNA, S. P. L.; SCHAUVLIEGE, S. Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A systematic review (2005-2017). JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, v. 41, n. 2, p. 205-217, APR 2018. Web of Science Citations: 3.
GOZALO-MARCILLA, MIGUEL; LUNA, STELIO P. L.; CROSIGNANI, NADIA; PUOLI FILHO, JOSE N. P.; POSSEBON, FABIO S.; PELLIGAND, LUDOVIC; TAYLOR, POLLY M. Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses. VETERINARY ANAESTHESIA AND ANALGESIA, v. 44, n. 5, p. 1116-1127, SEP 2017. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.