Pharmacokinetics, electrophysiological, and morphological effects of the intravitreal injection of mycophenolic acid in rabbits.
OBJECTIVE
To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA.


METHODS
Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 μg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy.


RESULTS
MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 μg and higher on day 30, while eyes injected with 100 μg presented the same changes already from day 15. No morphological change was found.


CONCLUSIONS
MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 μg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 μg may be safe for intravitreal use in rabbits.
1 Department of Ophthalmology, Medical School, Universidade de São Paulo (USP) , São Paulo SP, Brazil .
Fabio
F
Gasparin
Renata Genaro
RG
Aguiar
Gabriela Lourençon
GL
Ioshimoto
Armando
A
Silva-Cunha
Silvia Ligório
SL
Fialho
André Mauricio
AM
Liber
Balázs Vince
BV
Nagy
Nestor Norio
NN
Oiwa
Marcelo Fernandes
MF
Costa
Christina
C
Joselevitch
Dora Fix
DF
Ventura
Francisco Max
FM
Damico
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena; D004596:Electroretinography; D006207:Half-Life; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D058449:Intravitreal Injections; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014822:Vitreous Body / Q000378:metabolism
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid