Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses

In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 °C, kept in the dark or subjected to room light,...

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Bibliographic Details
Published in:Journal of veterinary pharmacology and therapeutics 2008-12, Vol.31 (6), p.511-516
Main Authors: DOUGLAS, L.C, YI, N.Y, DAVIS, J.L, SALMON, J.H, GILGER, B.C
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - adverse effects
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - therapeutic use
antibiotics
aqueous humor
chemical concentration
Chromatography, High Pressure Liquid
conjunctiva
Dermatitis, Phototoxic
dosage
drug evaluation
drug injection
drug toxicity
electroretinography
eyes
histopathology
Horses
intravitreal injection
pharmacokinetics
photostability
Sirolimus - adverse effects
Sirolimus - pharmacokinetics
Sirolimus - therapeutic use
subconjunctival injection
Tissue Distribution
Uveitis - drug therapy
Uveitis - veterinary
vitreous humor
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Summary:In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 °C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post-injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post-injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.
ISSN:0140-7783
1365-2885
DOI:10.1111/j.1365-2885.2008.00986.x