Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses

Sabina Diez Bernal, Nicole Studer, Wolfgang Thormann, Claudia Spadavecchia, Olivier Levionnois

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration.

STUDY DESIGN: Prospective, experimental, nonrandomized trial.

ANIMALS: A total of 10 healthy adult warmblood horses.

METHODS: Romifidine (loading dose: 0.08 mg kg-1, infusion: 0.03 mg kg-1 hour-1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic-pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested.

RESULTS: A two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33).

CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalVeterinary Anaesthesia and Analgesia
Volume47
Issue number1
Early online date21 Sep 2019
DOIs
Publication statusE-pub ahead of print - 21 Sep 2019

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