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

Diez Bernal, Sabina; Studer, Nicole; Thormann, Wolfgang; Spadavecchia, Claudia; Levionnois, Olivier (2020). Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses. Veterinary anaesthesia and analgesia, 47(1), pp. 129-136. Elsevier 10.1016/j.vaa.2019.06.010

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Anaesthesiology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Dìez Bernal, Sabina; Studer, Nicole; Thormann, Wolfgang; Spadavecchia, Claudia and Levionnois, Olivier

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1467-2995

Publisher:

Elsevier

Language:

English

Submitter:

Siegfried Hektor Hapfelmeier-Balmer

Date Deposited:

21 Jan 2020 14:57

Last Modified:

21 Jan 2020 14:57

Publisher DOI:

10.1016/j.vaa.2019.06.010

PubMed ID:

31810766

Uncontrolled Keywords:

antinociception electrical stimulation horses nociceptive withdrawal reflex pharmacokinetics romifidine

BORIS DOI:

10.7892/boris.138182

URI:

https://boris.unibe.ch/id/eprint/138182

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