Pharmacokinetics, Electrophysiological, and Morphological Effects of the Intravitreal Injection of Mycophenolic Acid in Rabbits

Autor(es):Mostrar menos -

Gasparin, Fabio ^[1] ; Aguiar, Renata Genaro ^[2] ; Ioshimoto, Gabriela Lourencon ^[2] ; Silva-Cunha, Armando ^[3] ; Fialho, Silvia Ligorio ^[4] ; Liber, Andre Mauricio ^[2] ; Nagy, Balazs Vince ^[2] ; Oiwa, Nestor Norio ^[2] ; Costa, Marcelo Fernandes ^[2] ; Joselevitch, Christina ^[2] ; Ventura, Dora Fix ^[2] ; Damico, Francisco Max ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Ophthalmol, BR-05403900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Psychol, Dept Expt Psychol, BR-05403900 Sao Paulo - Brazil

^[3] Univ Fed Minas Gerais, Fac Pharm, Belo Horizonte, MG - Brazil

^[4] Fundacao Ezequiel Dias FUNED, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS; v. 30, n. 6, p. 502-511, AUG 2014.
• Citações Web of Science: 5

Resumo

Purpose: 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 mu g) 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 mu g and higher on day 30, while eyes injected with 100 mu g 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 mu g MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 mu g may be safe for intravitreal use in rabbits. (AU)

• Processo FAPESP: 09/54292-7 - Avaliacao do desempenho visual em diferentes condicoes de iluminacao artificial com caracteristicas espectrais variadas
• Beneficiário: Balazs Vince Nagy
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 07/56624-1 - Estudo eletrofisiologico dos efeitos da injecao intravitrea de acido micofenolico (mpa) na retina de coelhos.
• Beneficiário: Renata Genaro Aguiar
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 07/02696-1 - Estudo farmacológico, morfológico e eletrofisiológico dos efeitos da injeção intravítrea de ácido micofenólico em coelhos
• Beneficiário: Dora Selma Fix Ventura
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/56844-1 - Estudo da eletrorretinografia do camundongo modelo de Alzheimer (3xTg-AD)
• Beneficiário: Gabriela Lourençon Ioshimoto
• Modalidade de apoio: Bolsas no Brasil - Mestrado