{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:13:04Z","timestamp":1791267184544,"version":"4.1.0"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,13]],"date-time":"2021-06-13T00:00:00Z","timestamp":1623542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.ejpb.2021.06.003","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T13:28:21Z","timestamp":1623763701000},"page":"155-162","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"special_numbering":"C","title":["Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail: Tissue exposures in the rabbit eye"],"prefix":"10.1016","volume":"166","author":[{"given":"Anam","family":"Fayyaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati-Sisko","family":"Vellonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli-Pekka","family":"Ranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Toropainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Reinisalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Valtari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jooseppi","family":"Puranen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe D'Amico","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma M.","family":"Heikkinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Ruponen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arto","family":"Urtti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Jamei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"del Amo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejpb.2021.06.003_b0005","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejps.2020.105553","article-title":"Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in rabbits","volume":"155","author":"Fayyaz","year":"2020","journal-title":"Eur. J. Pharmaceut. Sci.: Off. J. Eur. Federation Pharmaceut. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0010","article-title":"Comprehensive ocular and systemic pharmacokinetics of brinzolamide in rabbits after intracameral, topical, and intravenous administration","author":"Naageshwaran","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0015","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1023\/A:1018964823193","article-title":"Characterization of ocular pharmacokinetics of beta-blockers using a diffusion model after instillation","volume":"16","author":"Yamamura","year":"1999","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejpb.2021.06.003_b0020","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jps.2600680606","article-title":"Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits","volume":"68","author":"Lee","year":"1979","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0025","first-page":"59","article-title":"Precorneal, corneal, and postcorneal factors","volume":"58","author":"Lee","year":"1993","journal-title":"Drugs Pharmaceut. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0030","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0039-6257(93)90141-S","article-title":"Minimizing systemic absorption of topically administered ophthalmic drugs","volume":"37","author":"Urtti","year":"1993","journal-title":"Surv. Ophthalmol."},{"key":"10.1016\/j.ejpb.2021.06.003_b0035","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/jps.2600721108","article-title":"Corneal penetration behavior of \u03b2-blocking agents III. In Vitro\u2013In Vivo correlations","volume":"72","author":"Huang","year":"1983","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0040","first-page":"504","article-title":"Clinical pharmacokinetics of the eye","volume":"21","author":"Mishima","year":"1981","journal-title":"Proctor lecture, Investigative ophthalmology & visual science"},{"key":"10.1016\/j.ejpb.2021.06.003_b0045","doi-asserted-by":"crossref","unstructured":"R. Schoenwald, The importance of optimizing corneal penetration, in: Ophthalmic Drug Delivery, Springer, 1987, pp. 151-160. https:\/\/link.springer.com\/chapter\/10.1007\/978-1-4757-4175-9_15.","DOI":"10.1007\/978-1-4757-4175-9_15"},{"key":"10.1016\/j.ejpb.2021.06.003_b0050","first-page":"584","article-title":"Importance of the noncorneal absorption route in topical ophthalmic drug delivery","volume":"26","author":"Ahmed","year":"1985","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0055","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/jps.2600760802","article-title":"Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea","volume":"76","author":"Ahmed","year":"1987","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0060","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0002-9394(14)77735-9","article-title":"Penetration routes of topically applied eye medications","volume":"85","author":"Doane","year":"1978","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.ejpb.2021.06.003_b0065","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1089\/10807680152729257","article-title":"Drug delivery to the posterior segment of the eye: some insights on the penetration pathways after subconjunctival injection","volume":"17","author":"Lee","year":"2001","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"10.1016\/j.ejpb.2021.06.003_b0070","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejps.2018.03.034","article-title":"Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye","volume":"119","author":"Ramsay","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0075","first-page":"1827","article-title":"Improved ocular: systemic absorption ratio of timolol by viscous vehicle and phenylephrine","volume":"31","author":"Kyyr\u00f6nen","year":"1990","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0080","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0378-5173(84)90132-7","article-title":"Effect of ocular pigmentation on pilocarpine pharmacology in the rabbit eye. II. Drug response","volume":"19","author":"Urtti","year":"1984","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2021.06.003_b0085","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0378-5173(85)90005-5","article-title":"Systemic absorption of ocular pilocarpine is modified by polymer matrices","volume":"23","author":"Urtti","year":"1985","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2021.06.003_b0090","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1016\/j.xphs.2017.04.061","article-title":"Impact of chemical structure on conjunctival drug permeability: adopting porcine conjunctiva and cassette dosing for construction of in silico model","volume":"106","author":"Ramsay","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0095","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00004397-198002030-00004","article-title":"Structures and fluids involved in the penetration of topically applied drugs","volume":"20","author":"Maurice","year":"1980","journal-title":"Int. Ophthalmol. Clin."},{"key":"10.1016\/j.ejpb.2021.06.003_b0100","first-page":"332","article-title":"Permeability of the intraocular blood vessels","volume":"100","author":"Bill","year":"1980","journal-title":"Transactions of the ophthalmological societies of the United Kingdom"},{"key":"10.1016\/j.ejpb.2021.06.003_b0105","doi-asserted-by":"crossref","unstructured":"S.F. Nilsson, A. Alm, Determination of ocular blood flows with the microsphere method, in: Ocular Blood Flow, Springer, 2012, pp. 25-47. https:\/\/link.springer.com\/chapter\/10.1007\/978-3-540-69469-4_2.","DOI":"10.1007\/978-3-540-69469-4_2"},{"key":"10.1016\/j.ejpb.2021.06.003_b0110","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0014-4835(78)90086-6","article-title":"The fate of anterior chamber fluorescein in the monkey eye 1. the anterior chamber outflow pathways","volume":"27","author":"Sherman","year":"1978","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.ejpb.2021.06.003_b0115","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1021\/acs.molpharmaceut.9b00585","article-title":"Distribution of small molecular weight drugs into the porcine lens: Studies on imaging mass spectrometry, partition coefficients, and implications in ocular pharmacokinetics","volume":"16","author":"Heikkinen","year":"2019","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.ejpb.2021.06.003_b0120","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.2042-7158.1995.tb05726.x","article-title":"Penetration of \u03b2-Blockers through Ocular Membranes in A1bino Rabbits","volume":"47","author":"Sasaki","year":"1995","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.ejpb.2021.06.003_b0125","first-page":"627","article-title":"Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera","volume":"38","author":"H\u00e4m\u00e4l\u00e4inen","year":"1997","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0130","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jconrel.2004.07.001","article-title":"Model of transient drug diffusion across cornea","volume":"99","author":"Zhang","year":"2004","journal-title":"J. Control. Release"},{"key":"10.1016\/j.ejpb.2021.06.003_b0135","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.exer.2010.01.001","article-title":"Episcleral clearance of sodium fluorescein from a bioerodible sub-tenon's implant in the rat","volume":"90","author":"Chan","year":"2010","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.ejpb.2021.06.003_b0140","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1167\/iovs.05-0975","article-title":"Novel expression and characterization of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) by conjunctival cells","volume":"46","author":"Chen","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0145","first-page":"725","article-title":"Conjunctival and episcleral blood vessels are permeable to blood-borne horseradish peroxidase","volume":"24","author":"Raviola","year":"1983","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ejpb.2021.06.003_b0150","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ejpb.2015.01.003","article-title":"Intravitreal clearance and volume of distribution of compounds in rabbits: In silico prediction and pharmacokinetic simulations for drug development","volume":"95","author":"del Amo","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2021.06.003_b0155","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.preteyeres.2016.12.001","article-title":"Pharmacokinetic aspects of retinal drug delivery","volume":"57","author":"del Amo","year":"2017","journal-title":"Progress in retinal and eye research"},{"key":"10.1016\/j.ejpb.2021.06.003_b0160","first-page":"588","article-title":"Ocular Intracameral Pharmacokinetics for a Cocktail of Timolol","volume":"17","author":"Fayyaz","year":"2020","journal-title":"Betaxolol, and Atenolol in Rabbits, Mol Pharm"},{"key":"10.1016\/j.ejpb.2021.06.003_b0165","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.addr.2006.07.027","article-title":"Challenges and obstacles of ocular pharmacokinetics and drug delivery","volume":"58","author":"Urtti","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejpb.2021.06.003_b0170","first-page":"241","article-title":"Controlled drug delivery devices for experimental ocular studies with timolol 2","volume":"61","author":"Urtti","year":"1990","journal-title":"Ocular and systemic absorption in rabbits, International journal of pharmaceutics"},{"key":"10.1016\/j.ejpb.2021.06.003_b0175","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1007\/s11095-010-0132-8","article-title":"Prediction of the corneal permeability of drug-like compounds","volume":"27","author":"Kidron","year":"2010","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejpb.2021.06.003_b0180","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.2042-7158.1997.tb06768.x","article-title":"In-situ ocular absorption of ophthalmic beta-blockers through ocular membranes in albino rabbits","volume":"49","author":"Sasaki","year":"1997","journal-title":"The Journal of pharmacy and pharmacology"},{"key":"10.1016\/j.ejpb.2021.06.003_b0185","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/eye.1997.43","article-title":"The uveoscleral outflow routes","volume":"11","author":"Nilsson","year":"1997","journal-title":"Eye"},{"key":"10.1016\/j.ejpb.2021.06.003_b0190","first-page":"248","article-title":"Beta-adrenergic blockers: ocular penetration and binding to the uveal pigment","volume":"26","author":"Araie","year":"1982","journal-title":"Jpn. J. Ophthalmol."},{"key":"10.1016\/j.ejpb.2021.06.003_b0195","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1089\/jop.1995.11.489","article-title":"Comparison of concentration-time profiles of levobunolol and timolol in anterior and posterior ocular tissues of albino rabbits","volume":"11","author":"Acheampong","year":"1995","journal-title":"J. Ocul. Pharmacol. Ther."}],"container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641121001703?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641121001703?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T16:44:35Z","timestamp":1760546675000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0939641121001703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":39,"alternative-id":["S0939641121001703"],"URL":"https:\/\/doi.org\/10.1016\/j.ejpb.2021.06.003","relation":{},"ISSN":["0939-6411"],"issn-type":[{"value":"0939-6411","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail: Tissue exposures in the rabbit eye","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutics and Biopharmaceutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejpb.2021.06.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}