FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Equine veterinary journal2021; 54(5); 965-972; doi: 10.1111/evj.13526

Penetration of topically administered dexamethasone disodium phosphate and prednisolone acetate into the normal equine ocular fluids.

Abstract: Topical dexamethasone and prednisolone are currently the mainstay treatment for equine ophthalmic inflammatory diseases, such as equine recurrent uveitis. Comparative pharmacokinetic studies in horses are lacking and current guidelines are mainly based on empirical data and extrapolation from other species. Objective: To investigate the penetration and local concentrations of topically applied dexamethasone and prednisolone in normal equine ocular fluids and serum. Methods: Prospective randomised experimental pharmacokinetic study. Methods: Twenty-one Shetland ponies without ophthalmic disease were treated bilaterally topically every 2 hours during 24 hours to obtain steady state drug concentrations. One eye was treated with 0.15 mg of dexamethasone disodium phosphate (0.1%), and the other eye was simultaneously treated with 1.5 mg of prednisolone acetate (1%). Serum samples were taken prior to the induction of general anaesthesia. Aqueous and vitreous humour samples were taken during euthanasia at time points after administration of the last dose (t = 5 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min). Each pony was randomly assigned to one time point, and three ponies were sampled per time point. Dexamethasone and prednisolone concentrations were measured by liquid chromatography-mass spectrometry. Results: The mean dexamethasone concentration in aqueous humour was 32.4 ng/mL (standard deviation [SD] 10.9) and the mean prednisolone concentration was 321.6 ng/mL (SD 96.0). In the vitreous and in serum samples concentrations of both corticosteroids were below the limit of detection (LOD 2.5 ng/mL). Conclusions: The study group was limited to subjects without evidence of current ophthalmic disease. A limited number of time points were measured. Conclusions: Potentially effective dexamethasone and prednisolone concentrations were measured in the anterior chamber, but vitreal concentrations were negligible. Systemic uptake was low. Therefore, treatment with only topically administered corticosteroids is deemed insufficient in horses in cases of posterior uveitis. Further studies evaluating other routes of administration are warranted.
© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Get Full Text
Publication Date: 2021-11-21 PubMed ID: 34706129PubMed Central: PMC9545554DOI: 10.1111/evj.13526Google 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
  • Randomized Controlled Trial
  • Veterinary

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 focused on examining how effectively two types of corticosteroid eye drops, dexamethasone and prednisolone, penetrate the eye tissues of horses to treat inflammatory eye conditions. The study found that while these steroids could reach potentially effective concentrations in the anterior part of the eye, they could not do so in the back part, suggesting that treating posterior uveitis might require other administration methods.

Overview of the Research Methodology

  • The procedure was a prospective randomized pharmacokinetic study involving 21 Shetland ponies with no existing eye diseases.
  • Both eyes of each pony were given topical eye drops every two hours for 24 hours. One eye received dexamethasone drops, and the other received prednisolone drops.
  • Blood samples were taken before the ponies were anesthetized. The aqueous and vitreous humor (fluids inside the eye) were collected after euthanasia at specific time points.
  • Each pony was randomly assigned to one of the time points for fluid collection, ensuring three ponies were sampled at each time point.
  • The concentrations of dexamethasone and prednisolone in these samples were measured using liquid chromatography-mass spectrometry.

Research Findings

  • The concentration of dexamethasone in the anterior chamber (the front part of the eye) was found to be 32.4 ng/mL on average, while prednisolone averaged 321.6 ng/mL.
  • However, in both the vitreous humor (the back part of the eye) and the blood samples, the concentrations of the two drugs were undetectable (below the limit of detection of 2.5 ng/mL).

Conclusion and Implications

  • Because of the low detectable amounts in the posterior eye and systemically, the study concluded that only using topical eye drops of these corticosteroids might be insufficient for treating posterior uveitis in horses.
  • The researchers suggested further studies looking into different ways to administer these drugs for treating posterior uveitis, noting their study only included ponies without current eye diseases, and they only collected samples at a limited number of time-points.

Cite This Article

APA
Hermans H, van den Berg EMH, Slenter IJM, Vendrig DJC, de Nijs-Tjon LJL, Vernooij JCM, Brommer H, Boevé MH, Gehring R. (2021). Penetration of topically administered dexamethasone disodium phosphate and prednisolone acetate into the normal equine ocular fluids. Equine Vet J, 54(5), 965-972. https://doi.org/10.1111/evj.13526

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 5
Pages: 965-972

Researcher Affiliations

Hermans, Hanneke
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
van den Berg, Els M H
  • Dierenhospitaal Visdonk, Roosendaal, The Netherlands.
Slenter, Inge J M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Vendrig, Dax J C
  • Institute for Risk Assessment Sciences (IRAS), Division of Veterinary and Comparative Pharmacology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
de Nijs-Tjon, Lilian J L
  • Institute for Risk Assessment Sciences (IRAS), Division of Veterinary and Comparative Pharmacology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Vernooij, Johannes C M
  • Department of Population Health Sciences, Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Brommer, Harold
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Boevé, Michael H
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Gehring, Ronette
  • Institute for Risk Assessment Sciences (IRAS), Division of Veterinary and Comparative Pharmacology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

MeSH Terms

  • Animals
  • Dexamethasone
  • Eye Diseases / veterinary
  • Horse Diseases / drug therapy
  • Horses
  • Humans
  • Phosphates
  • Prednisolone / analogs & derivatives
  • Prospective Studies

Conflict of Interest Statement

No competing interests have been declared.

References

This article includes 40 references
  1. Gilger BC, Hollingsworth SR. Diseases of the uvea, uveitis and recurrent uveitis. In: Gilger BC, ed. Equine Ophthalmology. 3rd ed. John Wiley & Sons Incorporated; 2016:369–415.
  2. Malalana F, Stylianides A, McGowan C. Equine recurrent uveitis: Human and equine perspectives.. Vet J 2015 Oct;206(1):22-9.
    pubmed: 26188862doi: 10.1016/j.tvjl.2015.06.017google scholar: lookup
  3. McMullen RJ Jr, Fischer BM. Medical and Surgical Management of Equine Recurrent Uveitis.. Vet Clin North Am Equine Pract 2017 Dec;33(3):465-481.
    pubmed: 28985983doi: 10.1016/j.cveq.2017.07.003google scholar: lookup
  4. Fischer BM, McMullen RJ Jr, Reese S, Brehm W. Intravitreal injection of low-dose gentamicin for the treatment of recurrent or persistent uveitis in horses: Preliminary results.. BMC Vet Res 2019 Jan 16;15(1):29.
    pmc: PMC6335700pubmed: 30651102doi: 10.1186/s12917-018-1722-7google scholar: lookup
  5. Gilger BC, Michau TM. Equine recurrent uveitis: new methods of management.. Vet Clin North Am Equine Pract 2004 Aug;20(2):417-27, vii.
    pubmed: 15271431doi: 10.1016/j.cveq.2004.04.010google scholar: lookup
  6. Jordan VJ, Ireland JL, Rendle DI. Does oral prednisolone treatment increase the incidence of acute laminitis?. Equine Vet J 2017 Jan;49(1):19-25.
    pubmed: 26713748doi: 10.1111/evj.12565google scholar: lookup
  7. Awan MA, Agarwal PK, Watson DG, McGhee CN, Dutton GN. Penetration of topical and subconjunctival corticosteroids into human aqueous humour and its therapeutic significance.. Br J Ophthalmol 2009 Jun;93(6):708-13.
    pubmed: 19293163doi: 10.1136/bjo.2008.154906google scholar: lookup
  8. Loftsson T, Sigurdsson HH, Hreinsdóttir D, Konrádsdóttir F, Stefánsson E. Dexamethasone delivery to posterior segment of the eye. J Incl Phenom Macrocycl Chem 2007;57:585–9.
  9. Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC. Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate.. Ophthalmology 2002 Oct;109(10):1887-91.
    pubmed: 12359610doi: 10.1016/s0161-6420(02)01176-4google scholar: lookup
  10. Kaiser T, Werner A, Bäumer W, Kietzmann M. Tissue distribution of dexamethasone in canine ocular compartments following topical application of dexamethasone-21-isonicotinate and oxytetracycline HCl.. Vet Ophthalmol 2008 Sep-Oct;11(5):335-9.
    pubmed: 19046294doi: 10.1111/j.1463-5224.2008.00644.xgoogle scholar: lookup
  11. Bessonova J, Meyer-Lindenberg A, Bäumer W, Kietzmann M. Tissue distribution of dexamethasone in feline ocular structures following single topical application of dexamethasone as an ointment or suspension.. Vet Ophthalmol 2011 Mar;14(2):109-13.
    pubmed: 21366826doi: 10.1111/j.1463-5224.2010.00851.xgoogle scholar: lookup
  12. Chockalingam A, Xu L, Stewart S, LeMerdy M, Tsakalozou E, Fan J, Patel V, Rouse R. Protocol for evaluation of topical ophthalmic drug products in different compartments of fresh eye tissues in a rabbit model.. J Pharmacol Toxicol Methods 2019 Mar-Apr;96:9-14.
    pubmed: 30552958doi: 10.1016/j.vascn.2018.12.002google scholar: lookup
  13. McGhee CN, Watson DG, Midgley JM, Noble MJ, Dutton GN, Fern AI. Penetration of synthetic corticosteroids into human aqueous humour.. Eye (Lond) 1990;4 ( Pt 3):526-30.
    pubmed: 2209921doi: 10.1038/eye.1990.70google scholar: lookup
  14. Bäumer W, Reichenbecker F, Kietzmann M. Topische Arzneimittelanwendung am Pferdeauge unter besonderer Berücksichtung von Dexamethason. Praktischer Tierartz 2008;89:738–43.
  15. Weijtens O, Schoemaker RC, Lentjes EG, Romijn FP, Cohen AF, van Meurs JC. Dexamethasone concentration in the subretinal fluid after a subconjunctival injection, a peribulbar injection, or an oral dose.. Ophthalmology 2000 Oct;107(10):1932-8.
    pubmed: 11013202doi: 10.1016/s0161-6420(00)00344-4google scholar: lookup
  16. Hosseini K, Matsushima D, Johnson J, Widera G, Nyam K, Kim L, Xu Y, Yao Y, Cormier M. Pharmacokinetic study of dexamethasone disodium phosphate using intravitreal, subconjunctival, and intravenous delivery routes in rabbits.. J Ocul Pharmacol Ther 2008 Jun;24(3):301-8.
    pubmed: 18476800doi: 10.1089/jop.2007.0117google scholar: lookup
  17. Weijtens O, Feron EJ, Schoemaker RC, Cohen AF, Lentjes EG, Romijn FP, van Meurs JC. High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection.. Am J Ophthalmol 1999 Aug;128(2):192-7.
    pubmed: 10458175doi: 10.1016/s0002-9394(99)00129-4google scholar: lookup
  18. Weijtens O, Schoemaker RC, Cohen AF, Romijn FP, Lentjes EG, van Rooij J, van Meurs JC. Dexamethasone concentration in vitreous and serum after oral administration.. Am J Ophthalmol 1998 May;125(5):673-9.
    pubmed: 9625551doi: 10.1016/s0002-9394(98)00003-8google scholar: lookup
  19. Watson D, Noble MJ, Dutton GN, Midgley JM, Healey TM. Penetration of topically applied dexamethasone alcohol into human aqueous humor.. Arch Ophthalmol 1988 May;106(5):686-7.
    pubmed: 3358736doi: 10.1001/archopht.1988.01060130748037google scholar: lookup
  20. Leibowitz HM, Berrospi AR, Kupferman A, Restropo GV, Galvis V, Alvarez JA. Penetration of topically administered prednisolone acetate into the human aqueous humor.. Am J Ophthalmol 1977 Mar;83(3):402-6.
    pubmed: 848546doi: 10.1016/0002-9394(77)90740-1google scholar: lookup
  21. Stoppini R, Gilger BC. Equine ocular examination basic techniques. In: Gilger BC, ed. Equine Ophthalmology, 3rd ed. John Wiley & Sons Incorporated; 2016, 1–39.
  22. R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2020.
  23. Pinheiro J, Bates DM, DebRoy S, Sarkar D, R Core Team. Linear and Nonlinear Mixed Effects Models. R package version 3.1‐149. Vienna, Austria: R Foundation for Statistical Computing; 2020.
  24. Gaudio PA. A review of evidence guiding the use of corticosteroids in the treatment of intraocular inflammation.. Ocul Immunol Inflamm 2004 Sep;12(3):169-92.
    pubmed: 15385194doi: 10.1080/092739490500192google scholar: lookup
  25. McGhee CN, Noble MJ, Watson DG, Dutton GN, Fern AI, Healey TM, Midgley JM. Penetration of topically applied prednisolone sodium phosphate into human aqueous humour.. Eye (Lond) 1989;3 ( Pt 4):463-7.
    pubmed: 2606222doi: 10.1038/eye.1989.69google scholar: lookup
  26. Cagini C, Cometa F, Torroni G, Pellegrino A, Pellegrino R, Cavallini GM. Dexamethasone Disodium Phosphate Penetration Into the Human Aqueous Humor After Topical Application.. Curr Eye Res 2016 Jul;41(7):897-9.
    pubmed: 26580978doi: 10.3109/02713683.2015.1083589google scholar: lookup
  27. Regnier A. Clinical pharmacology and therapeutics. part 1: drug delivery and pharmacokinetics. In: Gelatt KN, Gilger BC, Kern TJ, eds. Veterinary Ophthalmology, 5th ed. John Wiley & Sons, Incorporated; 2013, 351–80.
  28. Ferguson DC, Hoenig M. Glucocorticoids, mineralocorticoids, and adrenolytic drugs. In: Riviere JE, Papich MG, eds. Veterinary Pharmacology and Therapeutics, 10th ed. John Wiley & Sons, Incorporated; 2018, 729–62.
  29. Asare K. Diagnosis and treatment of adrenal insufficiency in the critically ill patient.. Pharmacotherapy 2007 Nov;27(11):1512-28.
    pubmed: 17963461doi: 10.1592/phco.27.11.1512google scholar: lookup
  30. Nourry H, Viard C, Cambourieu C, Warnet JM. [A relevant choice for corticoid eye drops: solution or suspension?].. J Fr Ophtalmol 2011 Dec;34(10):691-6.
    pubmed: 22001623doi: 10.1016/j.jfo.2011.04.013google scholar: lookup
  31. Diestelhorst M, Kwon KA, Süverkrup R. Dose uniformity of ophthalmic suspensions.. J Cataract Refract Surg 1998 May;24(5):672-7.
    pubmed: 9610452doi: 10.1016/s0886-3350(98)80264-2google scholar: lookup
  32. Stringer W, Bryant R. Dose uniformity of topical corticosteroid preparations: difluprednate ophthalmic emulsion 0.05% versus branded and generic prednisolone acetate ophthalmic suspension 1%.. Clin Ophthalmol 2010 Oct 5;4:1119-24.
    pmc: PMC2952614pubmed: 20957058doi: 10.2147/opth.s12441google scholar: lookup
  33. Bar‐Ilan A, Neumann R. Basic considerations of ocular drug‐delivery systems. In: Zimmerman TJ, Kooner KS, Sharir M, Fechtner R, eds. Textbook of Ocular Pharmacology, 3rd ed. Lippincott‐Raven Publishers; 1997, 139–50.
  34. Kurihara A, Ojima F, Tsurufuji S. Chemotactic factor production by rat polymorphonuclear leukocytes: stimulation with opsonized zymosan particles and inhibition by dexamethasone.. Biochem Biophys Res Commun 1984 Mar 15;119(2):720-5.
    pubmed: 6712653doi: 10.1016/s0006-291x(84)80310-1google scholar: lookup
  35. Bachu RD, Chowdhury P, Al-Saedi ZHF, Karla PK, Boddu SHS. Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.. Pharmaceutics 2018 Feb 27;10(1).
    pmc: PMC5874841pubmed: 29495528doi: 10.3390/pharmaceutics10010028google scholar: lookup
  36. McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks.. Drug Saf 2002;25(1):33-55.
    pubmed: 11820911doi: 10.2165/00002018-200225010-00004google scholar: lookup
  37. Spiess BM, Nyikos S, Stummer E, Sahin A, Naegeli H. Systemic dexamethasone concentration in horses after continued topical treatment with an ophthalmic preparation of dexamethasone.. Am J Vet Res 1999 May;60(5):571-6.
    pubmed: 10328426
  38. Matthews AG. The lens and cataracts.. Vet Clin North Am Equine Pract 2004 Aug;20(2):393-415, vii.
    pubmed: 15271430doi: 10.1016/j.cveq.2004.04.009google scholar: lookup
  39. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.. Am J Ophthalmol 2005 Sep;140(3):509-16.
    pmc: PMC8935739pubmed: 16196117doi: 10.1016/j.ajo.2005.03.057google scholar: lookup
  40. Taylor SR, Isa H, Joshi L, Lightman S. New developments in corticosteroid therapy for uveitis.. Ophthalmologica 2010;224 Suppl 1:46-53.
    pubmed: 20714181doi: 10.1159/000318021google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.