Frontiers in veterinary science2022; 9; 951300; doi: 10.3389/fvets.2022.951300

Plasma atropine concentrations associated with decreased intestinal motility in horses.

Ekstrand, C
·
Michanek, P
·
Gehring, R
·
Sundell, A
·
Källse, A
·
Hedeland, M
·
Ström, L

Abstract: 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. Unassigned: 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. Unassigned: 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 nV7 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. Unassigned: 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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Publication Date: 2022-09-02 PubMed ID: 36118347PubMed Central: PMC9478751DOI: 10.3389/fvets.2022.951300Google Scholar: Lookup

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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines the effect of atropine, a medication commonly used in treating eye inflammation in horses, on the intestinal motility of the animal. The study reveals that frequent and high dosage of atropine can harm intestinal activity and cause abdominal discomfort in horses, but suggests safer dosing regimes.

Research Methodology

The research involved eight standardbred horses which were equally divided to either receive atropine or a saline solution as a control
The administered substance was infused over a period of 30 minutes in a cross-over design, allowing the horses to receive both treatments in alternating periods.
The concentrations of atropine in the plasma of the horses were determined via ultra-high-performance liquid chromatography and tandem mass spectrometry
Intestinal motility was evaluated using both borborygmi frequency, a measure of horses’ gut sounds, and electrointestinography (EIG), an electrical monitoring of the intestinal tract.
The recorded data was then analyzed through a non-linear mixed-effects model to understand the relationship between atropine concentrations and intestinal motility.

Research Findings

The results indicated that atropine significantly reduced both borborygmi and EIG responses which effectively translates to reduced intestine movement in horses.
Six out of the eight horses developed visible signs of abdominal pain, showing the potential negative impact atropine has on the animals’ comfort and wellbeing.
The pharmacokinetic results represented normalized rates of atropine dispersion and elimination in the horse’s body.
Similarly, pharmacodynamic findings indicated at what plasma concentration the drug triggers 50% of its maximum effect as well as the upper limit of the drug’s effect on cecal (attachment of large intestine to appendix) EIG response.
Through the use of this research data, six potentially safer dosing regimens, employing different frequency and dosage of topical atropine sulfate, were simulated.

Predictive Modelling and Suggestions

Using a combination of the research’s intravenous pharmacokinetic and pharmacodynamic data and the simulated dosing regimens, it was predicted that the administration of 1mg of topical atropine sulfate to the eye every hour or every 3 hours will result in the accumulation of atropine in the plasma, leading to a decrease in intestinal activity
Contrarily, the administration of the same amount every 6 hours was predicted to follow a safer dosing regimen for full-sized horses.
However, the conclusions rely heavily on clinical studies for full validation.
The research suggests alterations of the current treatment practices, encouraging the use of smaller droplet bottles to administer the topical atropine sulfate, reducing the risk of colic and similar conditions in smaller equids and horses.

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APA

Ekstrand C, Michanek P, Gehring R, Sundell A, Källse A, Hedeland M, Ström L. (2022). Plasma atropine concentrations associated with decreased intestinal motility in horses. Front Vet Sci, 9, 951300. https://doi.org/10.3389/fvets.2022.951300

Publication

Frontiers in veterinary science

ISSN: 2297-1769

NlmUniqueID: 101666658

Country: Switzerland

Language: English

Volume: 9

Pages: 951300

PII: 951300

Researcher Affiliations

Ekstrand, Carl

Department of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Michanek, Peter

Department of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Gehring, Ronette

Department of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Department of Population Health Sciences, Division of Veterinary and Comparative Pharmacology, Utrecht University, Utrecht, Netherlands.

Sundell, Anna

Department of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Källse, Annika

Department of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Hedeland, Mikael

Department of Medicinal Chemistry, Division of Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.

Ström, Lena

Department of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JM declared a past collaboration with the author RG.