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The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of Open Access research papers by Strathclyde researchers, including by researchers from the European Policies Research Centre (EPRC).

EPRC is a leading institute in Europe for comparative research on public policy, with a particular focus on regional development policies. Spanning 30 European countries, EPRC research programmes have a strong emphasis on applied research and knowledge exchange, including the provision of policy advice to EU institutions and national and sub-national government authorities throughout Europe.

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Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye

Koeberle, M. and Hughes, P.M. and Skellern, G.G. and Wilson, C.G. (2006) Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye. Pharmaceutical Research, 23. pp. 2781-2798. ISSN 0724-8741

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Abstract

Purpose. To develop an improved (1This is to clearly acknowledge that we have tried to improve an existing model.) arterially perfused bovine eye model and investigate the general ocular disposition of memantine. Materials and Methods. Fresh bovine eyes were prepared by exposing and cannulating one ciliary artery, placing the eye into a perfusion chamber and slowly increasing the rate of perfusion to 1.0 ml/min. Analysis of the arterial perfusion pressure (APP), intraocular pressure (IOP), venous perfusate for glucose consumption and lactate dehydrogenase (LDH) activity, and histopathology ensured viability. Memantine was administered with the perfusate (simulated systemic access), by an intravitreal injection and by topical infusion. At the appropriate time points, the cornea, aqueous humour, sclera, iris-ciliary body, choroid/RPE, retina and vitreous humour were harvested and analysed for memantine. Results. The preparation remained viable for at least 9 h. At this time, histopathological examination showed mild to moderate deterioration of retinal layers. However, all retinal layers remained well defined and the integrity of the inner limiting membrane and Bruch_s membrane were preserved. Glucose consumption, LDH levels and constant APP and IOP showed that correct cannulation and viability was maintained. After administration, memantine accumulated in the melanin rich iris-ciliary body and choroid/RPE. Results following topical administration indicate that substantial concentrations of memantine are present in the retina and choroid/RPE. Conclusions. The arterial perfused bovine eye system proved to be a useful system for ocular drug delivery studies. The experimental results indicate that memantine will accumulate in the posterior segment when delivered by the topical route and that melanin-binding may support sustaining significant concentrations in the retina