FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / BMC Vet Res / Topical ophthalmic atropine in horses, pharmacokinetics and ...
BMC veterinary research2021; 17(1); 149; doi: 10.1186/s12917-021-02847-4

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

Abstract: 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.
Get Full Text
Publication Date: 2021-04-07 PubMed ID: 33827566PubMed Central: PMC8028730DOI: 10.1186/s12917-021-02847-4Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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 study focuses on researching the effects and pharmacokinetics of atropine sulfate, popularly used in treating equine uveitis, when applied topically on horses. The research further investigates possible side effects, like decreased intestinal motility and colic, linked to the systemic exposure due to frequent administration of the drug.

Administration of Atropine Sulfate and Data Collection

  • Atropine sulfate was administered in two different ways – intravenously and topically – to a group of six horses. The topical method had two variations: manual application as eye drops and through a subpalpebral lavage system.
  • Blood samples were regularly collected post the drug administration to measure the atropine plasma concentration. The data was collected with the help of UHPLC-MS/MS.
  • The concentration of atropine was found to be below 0.05 μg/L (the lower limit of quantification) within five hours for both application methods.

Calculation of Pharmacokinetic Parameters

  • With the help of population compartmental modeling, various pharmacokinetic parameters like volume of distribution at steady-state, total plasma clearance, bioavailability, and terminal half-life were calculated.
  • Steady-state volume of distribution was found to be 1.7 L/kg while the total plasma clearance was 1.9 L/h‧kg.
  • The bioavailability following ophthalmic application as eye drops or topical infusions were 69% and 68%, respectively.
  • The terminal half-life of atropine was found to be short, measured at 0.8 hours.

Assessment of Atropine’s Effect on Gut Motility

  • In the second part of the study, the scientists investigated the effect of atropine on the gastro-intestinal motility of horses.
  • They used borborygmi-frequency, which is monitored using auscultation, to estimate gut motility.
  • The results showed a significant decrease in gut motility in horses when 1 mg of atropine was applied every three hours as opposed to the control. However, no such effect was seen when the drug was applied every six hours.
  • Interestingly, no signs of colic were observed under any of the experimental conditions.

Conclusions

  • Upon analyzing the plasma exposure data, the researchers concluded that administrating atropine at one-hour to three-hour intervals over 24 hours can lead to the drug’s accumulation in the plasma.
  • If the administration interval is increased to six hours, total atropine washout between subsequent applications can be achieved.
  • Simultaneous constant corneal and conjunctival atropine exposure can be safely maintained by applying a topical constant rate infusion at 5 μg/kg/24 h.

Cite This Article

APA
Ström L, Dalin F, Domberg M, Stenlund C, Bondesson U, Hedeland M, Toutain PL, Ekstrand C. (2021). Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility. BMC Vet Res, 17(1), 149. https://doi.org/10.1186/s12917-021-02847-4

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 17
Issue: 1
Pages: 149

Researcher Affiliations

Ström, L
  • Department of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Dalin, F
  • Department of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Domberg, M
  • Department of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Stenlund, C
  • Department of Clinical Sciences, Division of Large Animal Surgery, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Bondesson, U
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute, Uppsala, Sweden.
  • Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Hedeland, M
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute, Uppsala, Sweden.
  • Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
Toutain, P-L
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
  • The Royal Veterinary College, University of London, London, UK.
Ekstrand, C
  • Department of Biomedicine and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, P.O. Box 7028, SE-750 07, Uppsala, Sweden. carl.ekstrand@slu.se.

MeSH Terms

  • Animals
  • Atropine / administration & dosage
  • Atropine / blood
  • Atropine / pharmacokinetics
  • Biological Availability
  • Female
  • Gastrointestinal Motility / drug effects
  • Half-Life
  • Horses / blood
  • Injections, Intravenous
  • Male
  • Ophthalmic Solutions
  • Parasympatholytics / administration & dosage
  • Parasympatholytics / blood
  • Parasympatholytics / pharmacokinetics

Conflict of Interest Statement

The authors declare that they have no conflict of interest.

References

This article includes 27 references
  1. Gerding JC, Gilger BC. Prognosis and impact of equine recurrent uveitis.. Equine Vet J 2016;48(3):290–298.
    doi: 10.1111/evj.12451pubmed: 25891653google scholar: lookup
  2. Gilger BC. Equine recurrent uveitis: the viewpoint from the USA.. Equine Vet J 2010;42(S37):57–61.
    doi: 10.1111/j.2042-3306.2010.tb05636.xpubmed: 20939168google scholar: lookup
  3. Spiess BM. Equine recurrent uveitis: the European viewpoint.. Equine Vet J 2010;42(S37):50–56.
    doi: 10.1111/j.2042-3306.2010.tb05635.xpubmed: 20939167google scholar: lookup
  4. Davis JL, Stewart T, Brazik E, Gilger BC. The effect of topical administration of atropine sulfate on the normal equine pupil: influence of age, breed and gender.. Vet Ophthalmol 2003;6(4):329–332.
    doi: 10.1111/j.1463-5224.2003.00315.xpubmed: 14641831google scholar: lookup
  5. Herring IP, Pickett JP, Champagne ES, Troy GC, Marini M. Effect of topical 1% atropine sulfate on intraocular pressure in normal horses.. Vet Ophthalmol 2000;3(2-3):139–143.
    doi: 10.1046/j.1463-5224.2000.00134.xpubmed: 11397296google scholar: lookup
  6. McLaughlin SA, Whitley RD, Gilger BC. Ophthalmic atropine in horses: is colic a serious problem?. Equine Vet Educ 1991;3(2):94–96.
    doi: 10.1111/j.2042-3292.1991.tb01482.xgoogle scholar: lookup
  7. Sandmeyer LS, Bauer BS, Grahn BH. Diagnostic ophthalmology. Anterior uveitis of the right eye.. Can Vet J 2013;54:897–898.
    pmc: PMC3743581pubmed: 24155500
  8. Williams LB, Pinard CL. Corneal ulcers in horses.. Compend Contin Educ Vet 2013;35:E4.
    pubmed: 23532729
  9. Ducharme NG, Fubini SL. Gastrointestinal complications associated with the use of atropine in horses.. J Am Vet Med Assoc 1983;182:229–231.
    pubmed: 6826443
  10. Adams SB, Lamar CH, Masty J. Motility of the distal portion of the jejunum and pelvic flexure in ponies: effects of six drugs.. Am J Vet Res 1984;45:795–799.
    pubmed: 6731996
  11. Roberts MC, Argenzio A. Effects of amitraz, several opiate derivatives and anticholinergic agents on intestinal transit in ponies.. Equine Vet J 1986;18(4):256–260.
    doi: 10.1111/j.2042-3306.1986.tb03620.xpubmed: 3758001google scholar: lookup
  12. Malone ED, Kannan MS, Brown DR, Turner TA, Trent AM. Adrenergic, cholinergic, and nonadrenergic-noncholinergic intrinsic innervation of the jejunum in horses.. Am J Vet Res 1999;60:898–904.
    pubmed: 10407487
  13. Donnellan CM, Page PC, Nurton JP, van den Berg JS, Guthrie AJ. Comparison of glycopyrrolate and atropine in ameliorating the adverse effects of imidocarb dipropionate in horses.. Equine Vet J 2013;45(5):625–629.
    doi: 10.1111/evj.12032pubmed: 23461655google scholar: lookup
  14. de Lagarde M, Rodrigues N, Chevigny M, Beauchamp G, Albrecht B, Lavoie JP. N-butylscopolammonium bromide causes fewer side effects than atropine when assessing bronchoconstriction reversibility in horses with heaves.. Equine Vet J 2014;46(4):474–478.
    doi: 10.1111/evj.12229pubmed: 24423012google scholar: lookup
  15. Menozzi A, Pozzoli C, Poli E, Bontempi G, Serventi P, Meucci V, Intorre L, Bertini S. Role of muscarinic receptors in the contraction of jejunal smooth muscle in the horse: an in vitro study.. Res Vet Sci 2017;115:387–392.
    doi: 10.1016/j.rvsc.2017.07.012pubmed: 28711697google scholar: lookup
  16. Williams MM, Spiess BM, Pascoe PJ, O'Grady M. Systemic effects of topical and subconjunctival ophthalmic atropine in the horse.. Vet Ophthalmol 2000;3(2-3):193–199.
    doi: 10.1046/j.1463-5224.2000.00118.xpubmed: 11397302google scholar: lookup
  17. Wehrman RF, Gemensky-Metzler AJ, Zibura AE, Nyhart AB, Chandler HL. Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses.. J Am Vet Med Assoc 2017;251(11):1324–1330.
    doi: 10.2460/javma.251.11.1324pubmed: 29154707google scholar: lookup
  18. Kumar S, Karki R, Meena M, Prakash T, Rajeswari T, Goli D. Reduction in drop size of ophthalmic topical drop preparations and the impact of treatment.. J Adv Pharm Technol Res 2011;2:192–194.
    doi: 10.4103/2231-4040.85540pmc: PMC3217709pubmed: 22171317google scholar: lookup
  19. Chen T, Ward DA. Tear volume, turnover rate, and flow rate in ophthalmologically normal horses.. Am J Vet Res 2010;71(6):671–676.
    doi: 10.2460/ajvr.71.6.671pubmed: 20513183google scholar: lookup
  20. Hinderling PH, Gundert-Remy U, Schmidlin O. Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. I: Pharmacokinetics. J Pharm Sci 1985;74:703–710.
    pubmed: 4032240
  21. Hinderling PH, Gundert-Remy U, Schmidlin O, Heinzel G. Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. II: Pharmacodynamics.. J Pharm Sci 1985;74:711–717.
    doi: 10.1002/jps.2600740703pubmed: 4032241google scholar: lookup
  22. Perlstein I, Stepensky D, Sapoznikov D, Hoffman A. Power spectral analysis of heart rate variability in rats as a quantitative tool in the PK-PD analysis of the parasympatholytic activity of atropine.. Pharm Res 2001;18(8):1220–1225.
    doi: 10.1023/A:1010995414541pubmed: 11587495google scholar: lookup
  23. European Medicinal Agency Comittee for Veterinary Medicinal Products. Atropine Summary Report.. 1998.
  24. Ruckenbusch Y, Bardon T, Cherbut C, Pairet M, Ferré JP. Smooth Muscle Pharmacology of the large Intestine.. Congress of the European Association for Veterinary Pharmacology and Toxicology. 1985.
  25. Toutain PL, Bousquet-Melou A. Plasma clearance.. J Vet Pharmacol Ther 2004;27(6):415–425.
    doi: 10.1111/j.1365-2885.2004.00605.xpubmed: 15601437google scholar: lookup
  26. Ringer SK, Schwarzwald CC, Portier KG, Ritter A, Bettschart-Wolfensberger R. Effects on cardiopulmonary function and oxygen delivery of doses of romifidine and xylazine followed by constant rate infusions in standing horses.. Vet J 2013;195(2):228–234.
    doi: 10.1016/j.tvjl.2012.06.036pubmed: 22841452google scholar: lookup
  27. Gasthuys F, De Moor A, Parmentier D. Haemodynamic changes during sedation in ponies.. Vet Res Commun 1990;14(4):309–327.
    doi: 10.1007/BF00350713pubmed: 2392824google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.