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Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility

Ström, Lena and Dalin, Frieda and Domberg, Monika and Stenlund, Susanne and Bondesson, U. and Hedeland, M. and Toutain, P.-L. and Ekstrand, Carl (2021). Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility. BMC Veterinary Research. 17 :1 , 149
[Research article]

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Abstract

BackgroundTopical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment.ResultsAtropine sulfate (1mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 mu g/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9L/h?kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols.ConclusionsTaking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 mu g/kg/24h offers a safe alternative.

Authors/Creators:Ström, Lena and Dalin, Frieda and Domberg, Monika and Stenlund, Susanne and Bondesson, U. and Hedeland, M. and Toutain, P.-L. and Ekstrand, Carl
Title:Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility
Series Name/Journal:BMC Veterinary Research
Year of publishing :2021
Volume:17
Number:1
Article number:149
Number of Pages:13
ISSN:1746-6148
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Other Veterinary Science
Keywords:Colic, Equine, Pharmacokinetics, Pharmacodynamics, Plasma disposition, Side effect, Systemic exposure
URN:NBN:urn:nbn:se:slu:epsilon-p-111593
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-111593
Additional ID:
Type of IDID
DOI10.1186/s12917-021-02847-4
Web of Science (WoS)000638000800005
ID Code:28423
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:05 Jul 2022 13:25
Metadata Last Modified:05 Jul 2022 13:31

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