April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Evaluation of the Intraocular Toxicity and Pharmacokinetics of Intravitreal Candesartan
Author Affiliations & Notes
  • H. Park
    Ophthalmology, Pusan National University Hospital, Busan, Republic of Korea
  • D. Lim
    Lim's Eye Clinic, Busan, Republic of Korea
  • J. Shin
    Ophthalmology, Pusan National University Hospital, Busan, Republic of Korea
  • S. Lee
    Ophthalmology, Pusan National University Hospital, Busan, Republic of Korea
  • J. Lee
    Ophthalmology, Pusan National University Hospital, Busan, Republic of Korea
  • B. Oum
    Ophthalmology, Pusan National University Hospital, Busan, Republic of Korea
  • G. Koo
    Ophthalmology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
  • Footnotes
    Commercial Relationships  H. Park, None; D. Lim, None; J. Shin, None; S. Lee, None; J. Lee, None; B. Oum, None; G. Koo, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5108. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To investigate the intravitreal toxicity and pharmacokinetics of candesartan, a selective type I angiotensin II receptor blocker, in the rabbit eyes.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: drug toxicity/drug effects • ocular irritancy/toxicity testing • vitreous 
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