Pilot Study of the Safety and Tolerability of a Subconjunctival Penciclovir Implant in Cats Experimentally Infected with Herpesvirus

Jill C. Covert, Sara M Thomasy, Helen Kado-Fong, Leslie N. Kon, Philip H Kass, Christopher M. Reilly, Michael R. Lappin, Barry J. Margulies, David J Maggs

Research output: Contribution to journalArticle

Abstract

Purpose: To assess safety and tolerability of a subconjunctival penciclovir implant in cats infected with feline herpesvirus type 1 (FHV-1). Methods: Subconjunctival blank (n = 4 cats) or penciclovir-impregnated (n = 6) silicone implants were placed bilaterally in 10 normal, FHV-1-naive cats 7-8 days before viral inoculation. Outcomes included disease score, FHV-1 serology, conjunctival viral load, Schirmer tear tests (STT), tear film break-up times (TFBUTs), conjunctival histology, goblet cell density (GCD), body weight, tear and plasma penciclovir concentration, and corneal ulcer evaluation. Results: Both groups had similar clinical and histologic disease scores, STT values, TFBUTs, GCD, FHV-1 titers, viral loads, and body weight changes. No ocular or systemic signs of toxicity were noted. Tear penciclovir concentration varied widely among cats and across time points. Tear penciclovir concentrations exceeded the lowest published half maximal inhibitory concentration (IC50) in 5/6 treated cats. Plasma penciclovir concentrations remained below 10 ng/mL. Cats with higher tear penciclovir concentrations at inoculation and/or time of peak disease had fewer corneal ulcers than cats in which tear penciclovir concentrations were inconsistent, low, or unrecordable. Conclusions: Subconjunctival blank and penciclovir-impregnated implants were well tolerated at the ocular surface and not associated with systemic toxicity, adverse effect, or appreciable plasma penciclovir concentrations. Tear penciclovir concentrations >IC50 were sometimes achieved, especially during burst release soon after implant placement. Further study is necessary to determine efficacy of locally delivered penciclovir when penciclovir concentration is consistently maintained above IC50. This will be especially useful in patients unable to receive systemic therapy.

Original languageEnglish (US)
Pages (from-to)38-49
Number of pages12
JournalJournal of Ocular Pharmacology and Therapeutics
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Herpesviridae
Cats
Tears
Safety
Felidae
Inhibitory Concentration 50
Corneal Ulcer
Goblet Cells
Viral Load
penciclovir
Cell Count
Cat Diseases
Body Weight Changes
Silicones
Serology
Histology

Keywords

  • cat
  • herpes virus
  • penciclovir
  • preclinical pharmacology
  • subconjunctival implant

ASJC Scopus subject areas

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Pilot Study of the Safety and Tolerability of a Subconjunctival Penciclovir Implant in Cats Experimentally Infected with Herpesvirus. / Covert, Jill C.; Thomasy, Sara M; Kado-Fong, Helen; Kon, Leslie N.; Kass, Philip H; Reilly, Christopher M.; Lappin, Michael R.; Margulies, Barry J.; Maggs, David J.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 35, No. 1, 01.01.2019, p. 38-49.

Research output: Contribution to journalArticle

Covert, Jill C. ; Thomasy, Sara M ; Kado-Fong, Helen ; Kon, Leslie N. ; Kass, Philip H ; Reilly, Christopher M. ; Lappin, Michael R. ; Margulies, Barry J. ; Maggs, David J. / Pilot Study of the Safety and Tolerability of a Subconjunctival Penciclovir Implant in Cats Experimentally Infected with Herpesvirus. In: Journal of Ocular Pharmacology and Therapeutics. 2019 ; Vol. 35, No. 1. pp. 38-49.
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abstract = "Purpose: To assess safety and tolerability of a subconjunctival penciclovir implant in cats infected with feline herpesvirus type 1 (FHV-1). Methods: Subconjunctival blank (n = 4 cats) or penciclovir-impregnated (n = 6) silicone implants were placed bilaterally in 10 normal, FHV-1-naive cats 7-8 days before viral inoculation. Outcomes included disease score, FHV-1 serology, conjunctival viral load, Schirmer tear tests (STT), tear film break-up times (TFBUTs), conjunctival histology, goblet cell density (GCD), body weight, tear and plasma penciclovir concentration, and corneal ulcer evaluation. Results: Both groups had similar clinical and histologic disease scores, STT values, TFBUTs, GCD, FHV-1 titers, viral loads, and body weight changes. No ocular or systemic signs of toxicity were noted. Tear penciclovir concentration varied widely among cats and across time points. Tear penciclovir concentrations exceeded the lowest published half maximal inhibitory concentration (IC50) in 5/6 treated cats. Plasma penciclovir concentrations remained below 10 ng/mL. Cats with higher tear penciclovir concentrations at inoculation and/or time of peak disease had fewer corneal ulcers than cats in which tear penciclovir concentrations were inconsistent, low, or unrecordable. Conclusions: Subconjunctival blank and penciclovir-impregnated implants were well tolerated at the ocular surface and not associated with systemic toxicity, adverse effect, or appreciable plasma penciclovir concentrations. Tear penciclovir concentrations >IC50 were sometimes achieved, especially during burst release soon after implant placement. Further study is necessary to determine efficacy of locally delivered penciclovir when penciclovir concentration is consistently maintained above IC50. This will be especially useful in patients unable to receive systemic therapy.",
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AU - Thomasy, Sara M

AU - Kado-Fong, Helen

AU - Kon, Leslie N.

AU - Kass, Philip H

AU - Reilly, Christopher M.

AU - Lappin, Michael R.

AU - Margulies, Barry J.

AU - Maggs, David J

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AB - Purpose: To assess safety and tolerability of a subconjunctival penciclovir implant in cats infected with feline herpesvirus type 1 (FHV-1). Methods: Subconjunctival blank (n = 4 cats) or penciclovir-impregnated (n = 6) silicone implants were placed bilaterally in 10 normal, FHV-1-naive cats 7-8 days before viral inoculation. Outcomes included disease score, FHV-1 serology, conjunctival viral load, Schirmer tear tests (STT), tear film break-up times (TFBUTs), conjunctival histology, goblet cell density (GCD), body weight, tear and plasma penciclovir concentration, and corneal ulcer evaluation. Results: Both groups had similar clinical and histologic disease scores, STT values, TFBUTs, GCD, FHV-1 titers, viral loads, and body weight changes. No ocular or systemic signs of toxicity were noted. Tear penciclovir concentration varied widely among cats and across time points. Tear penciclovir concentrations exceeded the lowest published half maximal inhibitory concentration (IC50) in 5/6 treated cats. Plasma penciclovir concentrations remained below 10 ng/mL. Cats with higher tear penciclovir concentrations at inoculation and/or time of peak disease had fewer corneal ulcers than cats in which tear penciclovir concentrations were inconsistent, low, or unrecordable. Conclusions: Subconjunctival blank and penciclovir-impregnated implants were well tolerated at the ocular surface and not associated with systemic toxicity, adverse effect, or appreciable plasma penciclovir concentrations. Tear penciclovir concentrations >IC50 were sometimes achieved, especially during burst release soon after implant placement. Further study is necessary to determine efficacy of locally delivered penciclovir when penciclovir concentration is consistently maintained above IC50. This will be especially useful in patients unable to receive systemic therapy.

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