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  • Title: Intraocular toxicity and pharmacokinetics of candesartan in a rabbit model.
    Author: Lee JE, Lim DW, Park HJ, Shin JH, Lee SM, Oum BS.
    Journal: Invest Ophthalmol Vis Sci; 2011 May 02; 52(6):2924-9. PubMed ID: 21228384.
    Abstract:
    PURPOSE: To investigate the intravitreal toxicity and pharmacokinetics of candesartan, a selective type 1 angiotensin II receptor blocker, in rabbit eyes. METHODS: For the toxicity study, 15 white rabbits were divided into three groups (five rabbits each). Different candesartan doses, namely 0.5, 1, and 2 mg in 0.1 mL, were injected into the vitreous of the right eye in each of the five rabbits. The vehicle solution was injected into the left eye as a control. ERG was recorded at 1, 3, and 7 days after injection. Retinal histology was examined by light microscope and transmission electron microscope. For pharmacokinetics analysis, one eye of each of the 30 rabbits received an intravitreal injection of candesartan (1 mg/0.1 mL). The concentration of candesartan in the vitreous was measured by a liquid chromatograph-triple quadrupole mass spectrometer at 12, 24, 36, 48, 60, and 72 hours after injection. RESULTS: No significant difference in ERG was found between the study and the control eyes of the 0.5-mg group. The dark-adapted b-wave amplitudes decreased significantly at -10-dB intensities of stimulation in the 1-mg group. The b-wave amplitudes were significant at all intensities in the 2-mg group. Histologic studies revealed normal retinal morphology and structures in all eyes. The half-life of candesartan was 6.8 hours in the rabbit eyes. CONCLUSIONS: Intravitreal injection of 0.5 mg candesartan would be safe in the rabbit eyes. The half-life of candesartan was short in the vitreous, and modification of the delivery method would be required to extend the action duration for clinical applications.
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