Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility
Abstract Background Topical 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...
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| Format: | Article |
| Language: | English |
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BMC
2021-04-01
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| Series: | BMC Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s12917-021-02847-4 |
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| author | L. Ström F. Dalin M. Domberg C. Stenlund U. Bondesson M. Hedeland P-L Toutain C. Ekstrand |
| author_facet | L. Ström F. Dalin M. Domberg C. Stenlund U. Bondesson M. Hedeland P-L Toutain C. Ekstrand |
| author_sort | L. Ström |
| collection | DOAJ |
| description | Abstract Background Topical 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. Results Atropine sulfate (1 mg) 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 μg/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 1.7 L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9 L/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 (0.8 h). 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 1 mg 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. Conclusions Taking 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 24 h 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 μg/kg/24 h offers a safe alternative. |
| first_indexed | 2024-12-20T02:57:07Z |
| format | Article |
| id | doaj.art-5fdc0a9a401f4a3e83d53ee69f8fb49f |
| institution | Directory Open Access Journal |
| issn | 1746-6148 |
| language | English |
| last_indexed | 2024-12-20T02:57:07Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Veterinary Research |
| spelling | doaj.art-5fdc0a9a401f4a3e83d53ee69f8fb49f2022-12-21T19:55:52ZengBMCBMC Veterinary Research1746-61482021-04-0117111310.1186/s12917-021-02847-4Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motilityL. Ström0F. Dalin1M. Domberg2C. Stenlund3U. Bondesson4M. Hedeland5P-L Toutain6C. Ekstrand7Department of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural SciencesDepartment of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural SciencesDepartment of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural SciencesDepartment of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural SciencesDepartment of Chemistry, Environment and Feed Hygiene, National Veterinary InstituteDepartment of Chemistry, Environment and Feed Hygiene, National Veterinary InstituteINTHERES, Université de Toulouse, INRA, ENVTDepartment of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural SciencesAbstract Background Topical 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. Results Atropine sulfate (1 mg) 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 μg/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 1.7 L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9 L/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 (0.8 h). 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 1 mg 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. Conclusions Taking 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 24 h 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 μg/kg/24 h offers a safe alternative.https://doi.org/10.1186/s12917-021-02847-4ColicEquinePharmacokineticsPharmacodynamicsPlasma dispositionSide effect |
| spellingShingle | L. Ström F. Dalin M. Domberg C. Stenlund U. Bondesson M. Hedeland P-L Toutain C. Ekstrand Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility BMC Veterinary Research Colic Equine Pharmacokinetics Pharmacodynamics Plasma disposition Side effect |
| title | Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility |
| title_full | Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility |
| title_fullStr | Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility |
| title_full_unstemmed | Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility |
| title_short | Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility |
| title_sort | topical ophthalmic atropine in horses pharmacokinetics and effect on intestinal motility |
| topic | Colic Equine Pharmacokinetics Pharmacodynamics Plasma disposition Side effect |
| url | https://doi.org/10.1186/s12917-021-02847-4 |
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