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Abstract #91846 Published in IGR 21-4

Angiotensin Receptor Blockers in cyclodextrin nanoparticle eye drops: Ocular pharmacokinetics and pharmacologic effect on intraocular pressure

Lorenzo-Soler L; Olafsdottir OB; Garhöfer G; Jansook P; Kristinsdottir IM; Tan A; Loftsson T; Stefansson E
Acta Ophthalmologica 2021; 99: 376-382

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PURPOSE: Orally administered angiotensin II receptor blockers (ARBs) decrease intraocular pressure (IOP). Topical administration may reduce systemic side effects and result in a useful glaucoma drug. The aim of this study is to test the ocular delivery and pharmacologic effect of nanoparticle eye drops containing ARBs (e.g. irbesartan and candesartan). METHODS: 1.5% irbesartan and 0.15% candesartan eye drops were applied to rabbits. The pharmacokinetics in cornea and aqueous humour after single eye drop application were studied in 49 rabbits. The effect of the eye drops on IOP was studied in 10 rabbits using an iCare (® TonoVet Plus, iCare, Finland) tonometer and compared with 0.5% timolol eye drops. RESULTS: Candesartan lowered IOP from 24.6 ± 5.1 mmHg at baseline to 19.0 ± 2.9 mmHg (mean ± SD, p = 0.030, n = 10) 4 hr after application. Irbesartan lowered IOP from 24.2 ± 1.7 mmHg to 20.2 ± 0.9 mmHg (p = 0.14, n = 10). Timolol decreased the IOP from 24.9 ± 4.2 mmHg to 20.4 ± 4.8 mmHg (mean ± SD, p = 0.036, n = 10). The pharmacokinetics data show that both formulations deliver effective amounts of drug into the intraocular tissues, with irbesartan and candesartan reaching concentrations of 121 ± 69 and 30.43 ± 13.93 ng/g (mean ± SD), respectively, in the aqueous humour 3 hr after a single-dose administration. CONCLUSIONS: Topical application of irbesartan and candesartan eye drops delivers effective drug concentrations to the anterior segment of the eye in rabbits, achieving drug concentrations 100 times above the IC50 for angiotensin II receptor and showing an IOP-lowering effect. Angiotensin receptor blocker (ARB) eye drops have potential as a new class of glaucoma drugs.

Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

Full article

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
3.7 Biochemistry (Part of: 3 Laboratory methods)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)

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