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H. Park, D. Lim, J. Shin, S. Lee, J. Lee, B. Oum, G. Koo; Evaluation of the Intraocular Toxicity and Pharmacokinetics of Intravitreal Candesartan. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5108.
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To investigate the intravitreal toxicity and pharmacokinetics of candesartan, a selective type I angiotensin II receptor blocker, in the rabbit eyes.
All animals used in this study were treated in accordance with the institutional guidelines of Pusan National University and ARVO Statement for the Use of Animals Ophthalmic and Vision Research. For toxicity study, fifteen white rabbits were divided into three groups (5 rabbits each). Different candesartan doses, namely 0.5mg, 1mg, and 2mg in 0.1ml, were injected intravitreally into the right eye each of 5 rabbits. As a control, the vehicle solution was injected into the left eye of each animal. ERG recordings were made 1, 3, and 7 days after injection. Retinal histology was examined by light microscope and transmission electron microscope. For pharmacokinetics analysis, nine rabbits were divided into 3 groups (3 rabbits each). Each group received a 1mg intravitreal injection of candesartan.. The concentrations of candesartan in the vitreous were measured by using a Liquid Chromatograph-Triple Quadruple Mass Spectrometer at 24, 48, and 72 hours after intravitreal injection.
No significant difference in ERG was found between the study and the control eyes of the 0.5mg group. The scotopic and maximal b-wave amplitudes decreased significantly at -10dB intensities of stimulation in 1mg group. The ERG changes were significant at all intensities in the 2mg group. Histological studies revealed normal retinal morphology and structure in all eyes. The half-life of candesartan was approximately 9.9 hours in the rabbit eye.
Intravitreal injection of 0.5mg candesartan would be safe in the rabbit eyes. The half-life of candesartan was very short in the vitreous. Therefore, other delivery system for long action duration was further studied.
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