Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye

M. Koeberle, P.M. Hughes, G.G. Skellern, C.G. Wilson

Research output: Contribution to journalArticle

13 Citations (Scopus)

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
LanguageEnglish
Pages2781-2798
Number of pages18
JournalPharmaceutical Research
Volume23
DOIs
Publication statusPublished - 2006

Fingerprint

Memantine
Pharmacokinetics
Choroid
Perfusion
Retina
Ciliary Body
Melanins
Iris
Intraocular Pressure
L-Lactate Dehydrogenase
Arterial Pressure
Glucose 1-Dehydrogenase
Bruch Membrane
Membranes
Topical Administration
Vitreous Body
Sclera
Intravitreal Injections
Aqueous Humor
Drug Delivery Systems

Keywords

  • arterial perfused bovine eye
  • retinal
  • ocular drug delivery
  • memantine
  • melanin binding

Cite this

Koeberle, M. ; Hughes, P.M. ; Skellern, G.G. ; Wilson, C.G. / Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye. In: Pharmaceutical Research. 2006 ; Vol. 23. pp. 2781-2798.
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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 ciliaryartery, 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",
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Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye. / Koeberle, M.; Hughes, P.M.; Skellern, G.G.; Wilson, C.G.

In: Pharmaceutical Research, Vol. 23, 2006, p. 2781-2798.

Research output: Contribution to journalArticle

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T1 - Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye

AU - Koeberle, M.

AU - Hughes, P.M.

AU - Skellern, G.G.

AU - Wilson, C.G.

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N2 - 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 ciliaryartery, 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

AB - 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 ciliaryartery, 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

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