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Article
Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis
Journal of Ocular Pharmacology and Therapeutics
  • Lionel Sebbag, Iowa State University
  • Yuqi Yan, Iowa State University
  • Joe S. Smith, Iowa State University
  • Rachel A. Allbaugh, Iowa State University
  • Larry W. Wulf, Iowa State University
  • Jonathan P. Mochel, Iowa State University
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
5-9-2019
DOI
10.1089/jop.2019.0020
Abstract

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.

Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at selected times. Prednisone and prednisolone were quantified in tears by liquid chromatography-mass spectrometry.

Results: Lacrimal prednisone and prednisolone concentrations ranged from 2 to 523 ng/mL and 5 to 191 ng/mL, respectively. Drug concentrations were overall greater in dogs receiving higher doses of prednisone, but were not correlated with tear flow rate. Eyes with conjunctivitis often had larger amounts of prednisone and prednisolone in tear fluid compared to control eyes (up to +64%), but differences were not statistically significant. Significantly greater, but clinically insignificant, levels of prednisolone were found in eyes with severe versus mild conjunctivitis for oral prednisone doses ≥1.0 mg/kg.

Conclusions: Disruption of the blood–tear barrier with conjunctivitis did not significantly affect drug levels in tears. Based on drug PK in tears, oral prednisone is likely safe for the management of reflex uveitis and ocular surface diseases. However, further prospective trials using systemic corticotherapy in diseased animals are warranted to confirm findings from this preclinical study.

Comments

This is a manuscript of an article published as Sebbag, Lionel, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, and Jonathan P. Mochel. "Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis." Journal of Ocular Pharmacology and Therapeutics (2019). DOI: 10.1089/jop.2019.0020. Posted with permission.

Creative Commons License
Creative Commons Attribution 4.0
Copyright Owner
Lionel Sebbag et al.
Language
en
File Format
application/pdf
Citation Information
Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, et al.. "Tear Fluid Pharmacokinetics Following Oral Prednisone Administration in Dogs With and Without Conjunctivitis" Journal of Ocular Pharmacology and Therapeutics (2019)
Available at: http://0-works.bepress.com.library.simmons.edu/lionel-sebbag/11/