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Veterinary ophthalmology2018; 21(5); 516-523; doi: 10.1111/vop.12541

Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye.

Abstract: To determine if corneal epithelial cell integrity is detrimentally affected by short-term administration of 1.0% morphine sulfate. Additionally, we sought to determine if topical 1.0% morphine applied to the equine cornea would result in ocular or systemic absorption. Methods: Six healthy horses. Methods: Morphine sulfate (1.0%) was applied topically to one eye every four hours for 72 h before horses were euthanized. Serum samples were collected at varying time points during the study and aqueous and vitreous humor were collected immediately after euthanasia. Morphine quantification in serum, aqueous, and vitreous humor was performed by ELISA. Treated and control corneas were submitted for histopathology. Horses were monitored for adverse ocular and systemic effects throughout the study period. Results: All horses developed mild mucoid ocular discharge in the treated eye. One horse developed a fever during treatment. Morphine was detected in the aqueous humor of the treated eye for all horses with mean ± standard deviation of 165.18 ng/mL ± 87.69 ng/mL. Morphine was detected in vitreous humor of the treated eye of 5 of 6 horses with mean ± standard deviation of 4.87 ± 4.46 ng/mL. Morphine was detected in the serum of 5 of 6 horses at varying time points. Maximum systemic concentration reached in a single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in microscopic appearance between morphine-treated and control corneas. Conclusions: Topical administration of 1.0% morphine sulfate did not appear to cause any significant ocular or systemic adverse effects. Topical ophthalmic morphine application resulted in both ocular and systemic absorption.
Publication Date: 2018-01-19 PubMed ID: 29350477DOI: 10.1111/vop.12541Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper explores the effects and safety of topically applied 1.0% morphine sulfate on the eyes of healthy horses. It tries to understand if this treatment can damage the corneal epithelial cell or lead to ocular or systemic absorption.

Research Methodology

  • The team applied topical morphine sulfate (1.0%) to one eye of the six healthy horses. The application occurred every four hours for a span of 72 hours, after which the horses were euthanized.
  • The researchers collected serum samples at different stages during the study. Furthermore, they gathered the horse’s aqueous and vitreous humor (the fluids within the eye) immediately following euthanasia
  • They used Enzyme-Linked Immunosorbent Assays (ELISA) for morphine quantification in the aqueous, vitreous humor, and serum samples.
  • The study also checked for any adverse ocular (eye-related) or systemic effects throughout the experiment.
  • The researchers subsequently submitted the treated and control corneas for histopathology (microscopic examination of tissue to study disease).

Research Outcomes

  • All horses developed a mild ocular discharge in the eye that received treatment. However, it is not clear whether this discharge was a direct result of the morphine sulfate.
  • One horse also developed a fever during treatment.
  • Morphine sulfate was detected in the aqueous humor of the treated eye for all horses, signifying ocular absorption.
  • Morphine was found in the vitreous humor of 5 of the 6 horses, indicating that the drug had penetrated deeper into the eye.
  • Morphine was present in the serum of 5 out of the 6 horses. This result indicates that the morphine sulfate was absorbed systemically to some degree.
  • Lastly, no difference was found between the microscopic appearances of morphine-treated and control corneas. This result suggests that the short-term morphine treatment did not detrimentally affect the corneal epithelial cell integrity.

Conclusion

The team concluded that applying topical 1.0% morphine sulfate, at least in the short term, does not seem to cause significant adverse effects, either systemically or ocularly. Further, it signifies that the topical ophthalmic morphine application results in both ocular and systemic absorption.

Cite This Article

APA
Gordon E, Stang BV, Heidel J, Poulsen KP, Cebra CK, Schlipf JW. (2018). Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye. Vet Ophthalmol, 21(5), 516-523. https://doi.org/10.1111/vop.12541

Publication

ISSN: 1463-5224
NlmUniqueID: 100887377
Country: England
Language: English
Volume: 21
Issue: 5
Pages: 516-523

Researcher Affiliations

Gordon, Emma
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Stang, Bernadette V
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Heidel, Jerry
  • Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Poulsen, Keith P
  • Department of Medical Sciences, School of Veterinary Medicine and Wisconsin Veterinary Diagnostic Laboratory, University of Wisconsin-Madison, Madison, WI, USA.
Cebra, Christopher K
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
Schlipf, John W
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.

MeSH Terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics
  • Animals
  • Aqueous Humor / metabolism
  • Cornea / metabolism
  • Female
  • Horses / blood
  • Horses / metabolism
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacokinetics
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / pharmacokinetics
  • Reference Values
  • Treatment Outcome

Citations

This article has been cited 1 times.
  1. García-López C, Gómez-Huertas C, Sánchez-González JM, Borroni D, Rodríguez-Calvo-de-Mora M, Romano V, Rachwani-Anil R, Ramos-López JF, Ortiz-Pérez S, Rocha-de-Lossada C. Opioids and Ocular Surface Pathology: A Literature Review of New Treatments Horizons. J Clin Med 2022 Mar 4;11(5).
    doi: 10.3390/jcm11051424pubmed: 35268515google scholar: lookup