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Plasma atropine concentrations associated with decreased intestinal motility in horses

INTRODUCTION: Atropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk tha...

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Autores principales: Ekstrand, Carl, Michanek, Peter, Gehring, Ronette, Sundell, Anna, Källse, Annika, Hedeland, Mikael, Ström, Lena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478751/
https://www.ncbi.nlm.nih.gov/pubmed/36118347
http://dx.doi.org/10.3389/fvets.2022.951300
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author Ekstrand, Carl
Michanek, Peter
Gehring, Ronette
Sundell, Anna
Källse, Annika
Hedeland, Mikael
Ström, Lena
author_facet Ekstrand, Carl
Michanek, Peter
Gehring, Ronette
Sundell, Anna
Källse, Annika
Hedeland, Mikael
Ström, Lena
author_sort Ekstrand, Carl
collection PubMed
description INTRODUCTION: Atropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. MATERIALS AND METHODS: Eight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography–tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. RESULTS: Atropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg·h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 μg/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. CONCLUSION: The IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 μl of 1% atropine sulfate per drop or less may be used to lower the risk further.
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spelling pubmed-94787512022-09-17 Plasma atropine concentrations associated with decreased intestinal motility in horses Ekstrand, Carl Michanek, Peter Gehring, Ronette Sundell, Anna Källse, Annika Hedeland, Mikael Ström, Lena Front Vet Sci Veterinary Science INTRODUCTION: Atropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. MATERIALS AND METHODS: Eight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography–tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. RESULTS: Atropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg·h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 μg/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. CONCLUSION: The IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 μl of 1% atropine sulfate per drop or less may be used to lower the risk further. Frontiers Media S.A. 2022-09-02 /pmc/articles/PMC9478751/ /pubmed/36118347 http://dx.doi.org/10.3389/fvets.2022.951300 Text en Copyright © 2022 Ekstrand, Michanek, Gehring, Sundell, Källse, Hedeland and Ström. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Ekstrand, Carl
Michanek, Peter
Gehring, Ronette
Sundell, Anna
Källse, Annika
Hedeland, Mikael
Ström, Lena
Plasma atropine concentrations associated with decreased intestinal motility in horses
title Plasma atropine concentrations associated with decreased intestinal motility in horses
title_full Plasma atropine concentrations associated with decreased intestinal motility in horses
title_fullStr Plasma atropine concentrations associated with decreased intestinal motility in horses
title_full_unstemmed Plasma atropine concentrations associated with decreased intestinal motility in horses
title_short Plasma atropine concentrations associated with decreased intestinal motility in horses
title_sort plasma atropine concentrations associated with decreased intestinal motility in horses
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478751/
https://www.ncbi.nlm.nih.gov/pubmed/36118347
http://dx.doi.org/10.3389/fvets.2022.951300
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