{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:07:13Z","timestamp":1782122833210,"version":"3.54.5"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["AAPS PharmSciTech"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1208\/s12249-021-02050-6","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T16:03:02Z","timestamp":1621872182000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ocular Distribution of Papaverine Using Non-aqueous Vehicles"],"prefix":"10.1208","volume":"22","author":[{"given":"Priyanka","family":"Agarwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairam","family":"Behera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-5994","authenticated-orcid":false,"given":"Ilva Dana","family":"Rupenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"issue":"1","key":"2050_CR1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/0006-291X(70)91046-6","volume":"40","author":"L Triner","year":"1970","unstructured":"Triner L, Vulliemoz Y, Schwartz I, Nahas GG. Cyclic phosphodiesterase activity and the action of papaverine. Biochem Biophys Res Commun. 1970;40(1):64\u20139.","journal-title":"Biochem Biophys Res Commun"},{"issue":"7","key":"2050_CR2","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1111\/j.1755-3768.2008.01338.x","volume":"87","author":"H Resch","year":"2009","unstructured":"Resch H, Weigert G, Karl K, Pemp B, Garhofer G, Schmetterer L. Effect of systemic moxaverine on ocular blood flow in humans. Acta Ophthalmol. 2009;87(7):731\u20135.","journal-title":"Acta Ophthalmol"},{"issue":"2","key":"2050_CR3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.1755-3768.2010.01878.x","volume":"90","author":"B Pemp","year":"2012","unstructured":"Pemp B, Garhofer G, Lasta M, Schmidl D, Wolzt M, Schmetterer L. The effects of moxaverine on ocular blood flow in patients with age-related macular degeneration or primary open angle glaucoma and in healthy control subjects. Acta Ophthalmol. 2012;90(2):139\u201345.","journal-title":"Acta Ophthalmol"},{"issue":"1","key":"2050_CR4","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1186\/s12974-019-1649-3","volume":"16","author":"Y-Y Lee","year":"2019","unstructured":"Lee Y-Y, Park J-S, Leem Y-H, Park J-E, Kim D-Y, Choi Y-H, et al. The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson\u2019s disease mouse models. J Neuroinflamm. 2019;16(1):246.","journal-title":"J Neuroinflamm"},{"issue":"24","key":"2050_CR5","doi-asserted-by":"publisher","first-page":"4929","DOI":"10.1093\/hmg\/ddx373","volume":"26","author":"AK Yu","year":"2017","unstructured":"Yu AK, Datta S, McMackin MZ, Cortopassi GA. Rescue of cell death and inflammation of a mouse model of complex 1-mediated vision loss by repurposed drug molecules. Hum Mol Genet. 2017;26(24):4929\u201336.","journal-title":"Hum Mol Genet"},{"issue":"10","key":"2050_CR6","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1093\/hmg\/ddv045","volume":"24","author":"AK Yu","year":"2015","unstructured":"Yu AK, Song L, Murray KD, van der List D, Sun C, Shen Y, et al. Mitochondrial complex I deficiency leads to inflammation and retinal ganglion cell death in the Ndufs4 mouse. Hum Mol Genet. 2015;24(10):2848\u201360.","journal-title":"Hum Mol Genet"},{"key":"2050_CR7","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.mito.2016.08.002","volume":"30","author":"S Datta","year":"2016","unstructured":"Datta S, Tomilov A, Cortopassi G. Identification of small molecules that improve ATP synthesis defects conferred by Leber\u2019s hereditary optic neuropathy mutations. Mitochondrion. 2016;30:177\u201386.","journal-title":"Mitochondrion."},{"key":"2050_CR8","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1201\/9780203912072.ch11","volume-title":"Ophthalmic drug delivery systems","author":"I Ahmed","year":"2003","unstructured":"Ahmed I. The noncorneal route in ocular drug delivery. In: Mitra AK, editor. Ophthalmic drug delivery systems. New York: Marcel Dekker; 2003. p. 335\u201363."},{"issue":"4","key":"2050_CR9","doi-asserted-by":"publisher","first-page":"E820","DOI":"10.1208\/aapsj070479","volume":"7","author":"N Bodor","year":"2005","unstructured":"Bodor N, Buchwald P. Ophthalmic drug design based on the metabolic activity of the eye: soft drugs and chemical delivery systems. AAPS J. 2005;7(4):E820\u2013E33.","journal-title":"AAPS J"},{"key":"2050_CR10","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/978-3-642-69222-2_2","volume-title":"Pharmacology of the eye","author":"DM Maurice","year":"1984","unstructured":"Maurice DM, Mishima S. Ocular pharmacokinetics. In: Sears ML, editor. Pharmacology of the eye. Berlin: Springer Berlin Heidelberg; 1984. p. 19\u2013116."},{"issue":"Suppl 1","key":"2050_CR11","doi-asserted-by":"publisher","first-page":"S41","DOI":"10.1016\/S0039-6257(02)00326-0","volume":"47","author":"DM Maurice","year":"2002","unstructured":"Maurice DM. Drug delivery to the posterior segment from drops. Surv Ophthalmol. 2002;47(Suppl 1):S41\u201352.","journal-title":"Surv Ophthalmol"},{"issue":"3","key":"2050_CR12","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.jtos.2017.05.004","volume":"15","author":"JAP Gomes","year":"2017","unstructured":"Gomes JAP, Azar DT, Baudouin C, Efron N, Hirayama M, Horwath-Winter J, et al. TFOS DEWS II iatrogenic report. Ocul Surf. 2017;15(3):511\u201338.","journal-title":"Ocul Surf"},{"issue":"2","key":"2050_CR13","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1097\/IJG.0b013e31814b990d","volume":"17","author":"D Ghate","year":"2008","unstructured":"Ghate D, Edelhauser HF. Barriers to glaucoma drug delivery. J Glaucoma. 2008;17(2):147\u201356.","journal-title":"J Glaucoma"},{"issue":"6","key":"2050_CR14","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1097\/00061198-200312000-00008","volume":"12","author":"T Ishibashi","year":"2003","unstructured":"Ishibashi T, Yokoi N, Kinoshita S. Comparison of the short-term effects on the human corneal surface of topical timolol maleate with and without benzalkonium chloride. J Glaucoma. 2003;12(6):486\u201390.","journal-title":"J Glaucoma"},{"issue":"4","key":"2050_CR15","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1167\/iovs.16-20903","volume":"58","author":"S Datta","year":"2017","unstructured":"Datta S, Baudouin C, Brignole-Baudouin F, Denoyer A, Cortopassi GA. The eye drop preservative benzalkonium chloride potently induces mitochondrial dysfunction and preferentially affects LHON mutant cells. Invest Ophthalmol Vis Sci. 2017;58(4):2406\u201312.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2050_CR16","doi-asserted-by":"crossref","unstructured":"Agarwal P, Khun D, Kr\u00f6sser S, Eickhoff K, Wells FS, Willmott GR, et al. Preclinical studies evaluating the effect of semifluorinated alkanes on ocular surface and tear fluid dynamics. Ocul Surf. 2019.","DOI":"10.1016\/j.jtos.2019.02.010"},{"issue":"1","key":"2050_CR17","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.ijpharm.2018.01.019","volume":"538","author":"P Agarwal","year":"2018","unstructured":"Agarwal P, Scherer D, G\u00fcnther B, Rupenthal ID. Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs. Int J Pharm. 2018;538(1):119\u201329.","journal-title":"Int J Pharm"},{"issue":"8","key":"2050_CR18","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.1208\/s12249-018-1196-8","volume":"19","author":"DW Osborne","year":"2018","unstructured":"Osborne DW, Musakhanian J. Skin penetration and permeation properties of Transcutol\u00ae\u2014neat or diluted mixtures. AAPS PharmSciTech. 2018;19(8):3512\u201333.","journal-title":"AAPS PharmSciTech"},{"key":"2050_CR19","doi-asserted-by":"crossref","unstructured":"Box K, Comer J, Huque F. (2006), Correlations between PAMPA permeability and log P. In: Pharmacokinetic profiling in drug research. p. 243-57.","DOI":"10.1002\/9783906390468.ch15"},{"key":"2050_CR20","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ejpb.2019.06.008","volume":"142","author":"P Agarwal","year":"2019","unstructured":"Agarwal P, Craig JP, Kr\u00f6sser S, Eickhoff K, Swift S, Rupenthal ID. Topical semifluorinated alkane-based azithromycin suspension for the management of ocular infections. Eur J Pharm Biopharm. 2019;142:83\u201391.","journal-title":"Eur J Pharm Biopharm"},{"issue":"3","key":"2050_CR21","first-page":"501","volume":"55","author":"JF Griffith","year":"1980","unstructured":"Griffith JF, Nixon GA, Bruce RD, Reer PJ, Bannan EA. Dose-response studies with chemical irritants in the albino rabbit eye as a basis for selecting optimum testing conditions for predicting hazard to the human eye. Top Catal. 1980;55(3):501\u201313.","journal-title":"Top Catal"},{"issue":"3","key":"2050_CR22","first-page":"377","volume":"82","author":"JH Draize","year":"1944","unstructured":"Draize JH, Woodard G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1944;82(3):377\u201390.","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"2050_CR23","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1211\/jpp.58.1.0006","volume":"58","author":"Z Liu","year":"2006","unstructured":"Liu Z, Nie S, Guo H, Pan W, Li J. Effects of Transcutol P on the corneal permeability of drugs and evaluation of its ocular irritation of rabbit eyes. J Pharm Pharmacol. 2006;58(1):45\u201350.","journal-title":"J Pharm Pharmacol"},{"issue":"1","key":"2050_CR24","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ijpharm.2008.07.017","volume":"363","author":"X Li","year":"2008","unstructured":"Li X, Nie S-F, Kong J, Li N, Ju C-Y, Pan W-S. A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers. Int J Pharm. 2008;363(1):177\u201382.","journal-title":"Int J Pharm"},{"issue":"3","key":"2050_CR25","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3390\/pharmaceutics12030269","volume":"12","author":"R Varela-Fern\u00e1ndez","year":"2020","unstructured":"Varela-Fern\u00e1ndez R, D\u00edaz-Tom\u00e9 V, Luaces-Rodr\u00edguez A, Conde-Penedo A, Garc\u00eda-Otero X, Luzardo-\u00c1lvarez A, et al. Drug delivery to the posterior segment of the eye: biopharmaceutic and pharmacokinetic considerations. Pharmaceutics. 2020;12(3):269.","journal-title":"Pharmaceutics."},{"issue":"5","key":"2050_CR26","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.1016\/j.talanta.2011.08.060","volume":"85","author":"M Ghorbanzade","year":"2011","unstructured":"Ghorbanzade M, Fatemi MH, Karimpour M, Andersson PL. Quantitative and qualitative prediction of corneal permeability for drug-like compounds. Talanta. 2011;85(5):2686\u201394.","journal-title":"Talanta."},{"issue":"9","key":"2050_CR27","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1248\/bpb.b17-00288","volume":"40","author":"N Asano","year":"2017","unstructured":"Asano N, Wiseman JM, Tsuji F, Kawazu K. Limited azithromycin localization to rabbit meibomian glands revealed by LC-MS-based bioanalysis and DESI imaging. Biol Pharm Bull. 2017;40(9):1586\u20139.","journal-title":"Biol Pharm Bull"},{"issue":"12","key":"2050_CR28","doi-asserted-by":"publisher","first-page":"4890","DOI":"10.1021\/acs.molpharmaceut.9b00769","volume":"16","author":"P Jakubiak","year":"2019","unstructured":"Jakubiak P, Cantrill C, Urtti A, Alvarez-S\u00e1nchez R. Establishment of an in vitro\u2013in vivo correlation for melanin binding and the extension of the ocular half-life of small-molecule drugs. Mol Pharm. 2019;16(12):4890\u2013901.","journal-title":"Mol Pharm"},{"issue":"5","key":"2050_CR29","first-page":"373","volume":"14","author":"AN Shaaya","year":"1992","unstructured":"Shaaya AN, Kraus C, Bauman DH, Ritschel WA. Pharmacokinetics and bioavailability of papaverine HCl after intravenous, intracorporeal and penis topical administration in beagle dogs. J Ocul Pharmacol Ther. 1992;14(5):373\u20138.","journal-title":"J Ocul Pharmacol Ther"},{"issue":"7","key":"2050_CR30","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/bdd.2510120707","volume":"12","author":"C Kraus","year":"1991","unstructured":"Kraus C, Shaaya A, Ulmer J, Hutchings D, Menon A, Sakr A, et al. Pharmacokinetics and bioavailability of papaverine HCl following intravenous, peroral, rectal, vaginal, topical and buccal administration in beagle dogs. Biopharm Drug Dispos. 1991;12(7):537\u201346.","journal-title":"Biopharm Drug Dispos"},{"key":"2050_CR31","doi-asserted-by":"publisher","first-page":"912","DOI":"10.3109\/03639045.2011.633262","volume":"38","author":"MM Wen","year":"2011","unstructured":"Wen MM, El-kamel A, Khalil S. Systemic enhancement of papaverine transdermal gel for erectile dysfunction. Drug Dev Ind Pharm. 2011;38:912\u201322.","journal-title":"Drug Dev Ind Pharm"},{"key":"2050_CR32","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.addr.2017.09.008","volume":"126","author":"D Huang","year":"2018","unstructured":"Huang D, Chen YS, Rupenthal ID. Overcoming ocular drug delivery barriers through the use of physical forces. Adv Drug Deliv Rev. 2018;126:96\u2013112.","journal-title":"Adv Drug Deliv Rev"},{"issue":"3","key":"2050_CR33","first-page":"627","volume":"38","author":"KM Hamalainen","year":"1997","unstructured":"Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci. 1997;38(3):627\u201334.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"6","key":"2050_CR34","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s13346-016-0339-2","volume":"6","author":"V Agrahari","year":"2016","unstructured":"Agrahari V, Mandal A, Agrahari V, Trinh HM, Joseph M, Ray A, et al. A comprehensive insight on ocular pharmacokinetics. Drug Deliv Transl Res. 2016;6(6):735\u201354.","journal-title":"Drug Deliv Transl Res"},{"issue":"9","key":"2050_CR35","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/j.2042-7158.1991.tb03548.x","volume":"43","author":"R Panchagnula","year":"1991","unstructured":"Panchagnula R, Ritschel WA. Development and evaluation of an intracutaneous depot formulation of corticosteroids using Transcutol as a cosolvent: in-vitro, ex-vivo and in-vivo rat studies. J Pharm Pharmacol. 1991;43(9):609\u201314.","journal-title":"J Pharm Pharmacol"},{"issue":"3","key":"2050_CR36","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1089\/jop.2005.21.210","volume":"21","author":"U Becker","year":"2005","unstructured":"Becker U, Ehrhardt C, Schaefer UF, Gukasyan HJ, Kim K-J, Lee VH, et al. Tissue distribution of moxaverine\u2013hydrochloride in the rabbit eye and plasma. J Ocul Pharmacol Ther. 2005;21(3):210\u20136.","journal-title":"J Ocul Pharmacol Ther"},{"issue":"6","key":"2050_CR37","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1007\/s10384-014-0348-y","volume":"58","author":"Y Shibata","year":"2014","unstructured":"Shibata Y, Tanaka Y, Tomita T, Taogoshi T, Kimura Y, Chikama T, et al. Evaluation of corneal damage caused by iodine preparations using human corneal epithelial cells. Jpn J Ophthalmol. 2014;58(6):522\u20137.","journal-title":"Jpn J Ophthalmol"},{"issue":"1","key":"2050_CR38","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1023\/A:1013671819604","volume":"19","author":"M Kuwano","year":"2002","unstructured":"Kuwano M, Ibuki H, Morikawa N, Ota A, Kawashima Y. Cyclosporine A formulation affects its ocular distribution in rabbits. Pharm Res. 2002;19(1):108\u201311.","journal-title":"Pharm Res"},{"issue":"4","key":"2050_CR39","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.jpba.2010.01.015","volume":"52","author":"R Earla","year":"2010","unstructured":"Earla R, Boddu SH, Cholkar K, Hariharan S, Jwala J, Mitra AK. Development and validation of a fast and sensitive bioanalytical method for the quantitative determination of glucocorticoids--quantitative measurement of dexamethasone in rabbit ocular matrices by liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal. 2010;52(4):525\u201333.","journal-title":"J Pharm Biomed Anal"},{"issue":"3","key":"2050_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1167\/tvst.4.3.1","volume":"4","author":"K Cholkar","year":"2015","unstructured":"Cholkar K, Gilger BC, Mitra AK. Topical, aqueous, clear cyclosporine formulation design for anterior and posterior ocular delivery. Transl Vis Sci Techn. 2015;4(3):1.","journal-title":"Transl Vis Sci Techn"}],"container-title":["AAPS PharmSciTech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-021-02050-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1208\/s12249-021-02050-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-021-02050-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T17:07:04Z","timestamp":1627319224000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1208\/s12249-021-02050-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,24]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["2050"],"URL":"https:\/\/doi.org\/10.1208\/s12249-021-02050-6","relation":{},"ISSN":["1530-9932"],"issn-type":[{"value":"1530-9932","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,24]]},"assertion":[{"value":"2 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"160"}}