Angiotensin Receptor Blockers in cyclodextrin nanoparticle eye drops: Ocular pharmacokinetics and pharmacologic effect on intraocular pressure.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Olafsdottir, Olof Birna
Kristinsdottir, Iris Myrdal
MetadataShow full item record
CitationLorenzo-Soler L, Olafsdottir OB, Garhöfer G, Jansook P, Kristinsdottir IM, Tan A, Loftsson T, Stefansson E. Angiotensin Receptor Blockers in cyclodextrin nanoparticle eye drops: Ocular pharmacokinetics and pharmacologic effect on intraocular pressure. Acta Ophthalmol. 2020 Nov 16. doi: 10.1111/aos.14639.
AbstractPurpose: 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. Keywords: angiotensin receptor blockers; glaucoma; intraocular pressure; pharmacokinetics.
DescriptionTo access publisher's full text version of this article click on the hyperlink below
Rights© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
- γ-Cyclodextrin nanoparticle eye drops with dorzolamide: effect on intraocular pressure in man.
- Authors: Gudmundsdottir BS, Petursdottir D, Asgrimsdottir GM, Gottfredsdottir MS, Hardarson SH, Jóhannesson G, Kurkov SV, Jansook P, Loftsson T, Stefánsson E
- Issue date: 2014 Feb
- Differential effects of angiotensin II type I receptor blockers on reducing intraocular pressure and TGFβ signaling in the mouse retina.
- Authors: Hazlewood RJ, Chen Q, Clark FK, Kuchtey J, Kuchtey RW
- Issue date: 2018
- L-662,583 is a topically effective ocular hypotensive carbonic anhydrase inhibitor in experimental animals.
- Authors: Sugrue MF, Gautheron P, Mallorga P, Nolan TE, Graham SL, Schwam H, Shepard KL, Smith RL
- Issue date: 1990 Jan
- Effect of Eye Drops Containing Disulfiram and Low-Substituted Methylcellulose in Reducing Intraocular Pressure in Rabbit Models.
- Authors: Nagai N, Yoshioka C, Mano Y, Ito Y, Okamoto N, Shimomura Y
- Issue date: 2015
- Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension.
- Authors: Israili ZH
- Issue date: 2000 Apr