Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

Author(s)

Francisco Max Damico ^[1] ; Mariana Ramos Scolari ^[1] ; Gabriela Lourençon Ioshimoto ^[3] ; Beatriz Sayuri Takahashi ^[1] ; Armando da Silva Cunha Jr. ^[3] ; Sílvia Ligório Fialho ^[6] ; Daniela Maria Bonci ^[5] ; Fabio Gasparin ^[1] ; Dora Fix Ventura ^[5]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil

^[2] Universidade de São Paulo. Instituto de Psicologia - Brasil

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

^[4] Fundação Ezequiel Dias - Brasil

^[5] Univ Sao Paulo, Inst Psicol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Clinics; v. 67, n. 8, p. 931-937, 2012-08-00.

Abstract

OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina. (AU)

• FAPESP's process: 10/08331-8 - Study of acyclovir biological half-life on the rabbit vitreous after intravitreal injection and the influence of vitreous liquefaction by hyaluronidase
• Grantee: Mariana Ramos Scolari
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 11/06924-4 - Intravitreal acyclovir in rabbit eyes: a pharmacological, electrophysiological, immunocytochemical and morphological study
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/58731-2 - Vision as a sensitive indicator of conditions threatening retinal and central nervous system function
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Research Projects - Thematic Grants