Rabbit as an animal model for intravitreal pharmacokinetics : Clinical predictability and quality of the published data

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del Amo , E M & Urtti , A 2015 , ' Rabbit as an animal model for intravitreal pharmacokinetics : Clinical predictability and quality of the published data ' , Experimental Eye Research , vol. 137 , pp. 111-124 . https://doi.org/10.1016/j.exer.2015.05.003

Title: Rabbit as an animal model for intravitreal pharmacokinetics : Clinical predictability and quality of the published data
Author: del Amo, Eva M.; Urtti, Arto
Contributor: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
Date: 2015-08
Language: eng
Number of pages: 14
Belongs to series: Experimental Eye Research
ISSN: 0014-4835
URI: http://hdl.handle.net/10138/203409
Abstract: Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics. (C) 2015 The Authors. Published by Elsevier Ltd.
Subject: Ocular pharmacokinetics
Drug delivery
Intravitreal
Animal model
Rabbit
RETINAL-PIGMENT EPITHELIUM
ENDOTHELIAL GROWTH-FACTOR
MEDIATED DRUG DISPOSITION
INTRAOCULAR PHARMACOKINETICS
CYTOMEGALOVIRUS RETINITIS
NONVITRECTOMIZED EYES
MACULAR DEGENERATION
BLOOD-FLOW
POSTOPERATIVE ENDOPHTHALMITIS
OCULAR MICRODIALYSIS
3125 Otorhinolaryngology, ophthalmology
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