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T. Caillaud, P. Roy, K. Viaud, P.–P. Elena; Pharmacokinetics of Clonidine After Single Application of Transscleral Iontophoresis in Rabbits . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5109.
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To determine the pharmacokinetics of clonidine in rabbit eye tissues after single application of transscleral iontophoresis.
Anodal (+) iontophoresis was performed in pigmented rabbits (Fauve de Bourgogne) at 2 mA for 4 min using Eyegate applicator filled with 0.5ml of 0.25% 3H clonidine–HCl solution and compared with an application without current for 4 min and with a 50ml single instillation. The transscleral applicator has an annular shape of which, the proximal part diameter is slightly larger than the limbus while the distal part covers 2 mm of the anterior sclera behind the limbus. Rabbits (n=3/time–point) were euthanized at 0.5, 1, 6h after completion of iontophoresis. Following tissues of the treated eyes were sampled (15 specimens): bulbar conjunctiva, palpebral conjunctiva, nictitating membrane, cornea, aqueous humor, iris, ciliary body, lens, vitreous, retina, choroid, sclera, optic nerve, Harderian gland, and lacrimal gland. Also, body fluid whole blood and/or plasma was sampled to verify systemic uptake. Determination of clonidine equivalent concentrations in all samples was determined by liquid scintillation after chemical dissolution using a beta counter.
At the 0.5 hour, the clonidine level in eye tissues were enhanced by iontophoresis by a minimum of 5.2 times (iris) when compared to an application without current. Greater enhancements were seen in the sclera (42.1 times) and the choroid (20.3 times). Application without current was comparable to a single topical application. Clearance was comparable between delivery modes for all tissues with some tissues like choroid or ciliary body keeping their initial content over the sampling period, with tissue concentration in the choroid of 38.0±15.8 µg/g of structure at 6h (4.0±1.2 µg/g topically) and 41.7±7.6 µg/g (12.8±6.8 µg/g topically).
Transscleral delivery of alpha–2 adrenoreceptor agonist clonidine was enhanced by several folds by the iontophoretic current and tissue retention and half–life is independent from the current.
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