{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:35:49Z","timestamp":1786988149188,"version":"build-2736575974"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100013171","name":"Ryobi Teien Memory Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shujitsu University"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1016\/j.ejps.2018.01.032","type":"journal-article","created":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T08:36:34Z","timestamp":1517560594000},"page":"21-26","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":34,"special_numbering":"C","title":["The relationship between in vivo nasal drug clearance and in vitro nasal mucociliary clearance: Application to the prediction of nasal drug absorption"],"prefix":"10.1016","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-4331","authenticated-orcid":false,"given":"Daisuke","family":"Inoue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kiriyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemasa","family":"Katsumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Ogawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikiro","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Higaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Yutani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Sakane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Furubayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejps.2018.01.032_bb0005","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1023\/A:1018994807746","article-title":"Effects of pharmaceutical compounds on ciliary beating in human nasal epithelial cells: a comparative study of cell culture models","volume":"16","author":"Agu","year":"1999","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2018.01.032_bb0010","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1042\/cs058006Pa","article-title":"Lung mucociliary clearance in normal subjects during selective and non-selective b-adrenoceptor blockade","volume":"58","author":"Bateman","year":"1980","journal-title":"Clin. Sci."},{"key":"10.1016\/j.ejps.2018.01.032_bb0015","first-page":"938","article-title":"Topical tolerability of salmon calcitonin assessed by mucociliary transport velocity investigation","volume":"40","author":"Braga","year":"1990","journal-title":"Arzneimittelforschung"},{"key":"10.1016\/j.ejps.2018.01.032_bb0020","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/j.2042-7158.1992.tb03242.x","article-title":"The effects of calcitonin nasal preparations and their excipients on mucociliary clearance in an ex-vivo frog palate test","volume":"44","author":"Braga","year":"1992","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0025","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/S0006-3495(94)80864-1","article-title":"Stationary and nonstationary correlation-frequency analysis of heterodyne mode laser light scattering: magnitude and periodicity of canine tracheal ciliary beat frequency in vivo","volume":"66","author":"Chandra","year":"1994","journal-title":"Biophys. J."},{"key":"10.1016\/j.ejps.2018.01.032_bb0030","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1136\/adc.64.4.546","article-title":"Measurement of nasal mucociliary clearance","volume":"64","author":"Corbo","year":"1989","journal-title":"Arch. Dis. Child."},{"key":"10.1016\/j.ejps.2018.01.032_bb0035","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0952-0600(92)90068-R","article-title":"The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro","volume":"5","author":"Davalia","year":"1992","journal-title":"Pulm. Pharmacol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0040","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0378-5173(94)00274-9","article-title":"Drug effects on in vivo nasal clearance in rats","volume":"116","author":"Donovan","year":"1995","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.01.032_bb0045","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1152\/japplphysiol.00755.2001","article-title":"Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells","volume":"92","author":"Frohock","year":"2002","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0050","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1248\/bpb.30.608","article-title":"Evaluation of the contribution of the nasal cavity and gastrointestinal tract to drug absorption following nasal application to rats","volume":"30","author":"Furubayashi","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.ejps.2018.01.032_bb0055","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1248\/bpb.30.1007","article-title":"Kinetic model to predict the absorption of nasally applied drugs from in vitro transcellular permeability of drugs","volume":"30","author":"Furubayashi","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.ejps.2018.01.032_bb0060","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0034-5687(93)90039-D","article-title":"Cholinergic and adrenergic stimulation of mucociliary transport in the rat trachea","volume":"92","author":"Gatto","year":"1993","journal-title":"Respir. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0065","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1164\/ajrccm\/144.5.1042","article-title":"Influence of inhaled atropine on lung mucociliary function in humans","volume":"144","author":"Groth","year":"1991","journal-title":"Am. Rev. Respir. Dis."},{"key":"10.1016\/j.ejps.2018.01.032_bb0070","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.2042-7158.1985.tb05069.x","article-title":"Intranasal drug delivery by spray and drops","volume":"37","author":"Hardy","year":"1985","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0075","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1113\/expphysiol.2004.028746","article-title":"ATP regulation of ciliary beat frequency in rat tracheal and distal airway epithelium","volume":"90","author":"Hayashi","year":"2008","journal-title":"Exp. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0080","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0378-5173(81)90058-2","article-title":"Absorption of drugs from the nasal mucosa of rat","volume":"7","author":"Hirai","year":"1981","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.01.032_bb0085","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1001\/archotol.130.4.440","article-title":"Influence of preservatives and topical steroids on ciliary beat frequency in vitro","volume":"130","author":"Hofmann","year":"2004","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"10.1016\/j.ejps.2018.01.032_bb0090","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1097\/00004032-197506000-00011","article-title":"The removal of particles from the nasopharynx (NP) compartment of the respiratory tract by nose blowing and swabbing","volume":"28","author":"Hounam","year":"1975","journal-title":"Health Phys."},{"key":"10.1016\/j.ejps.2018.01.032_bb0095","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1034\/j.1399-3003.1999.14b35.x","article-title":"Effects of drugs on mucus clearance","volume":"14","author":"Houtmeyers","year":"1999","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.ejps.2018.01.032_bb0100","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0168-3659(02)00363-2","article-title":"Nasal drug delivery possibilities, problems and solutions","volume":"87","author":"Illum","year":"2003","journal-title":"J. Control. Release"},{"issue":"6","key":"10.1016\/j.ejps.2018.01.032_bb0105","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1248\/bpb.35.889","article-title":"In vitro evaluation of nasal mucociliary clearance using excised rat nasal septum","volume":"35","author":"Inoue","year":"2012","journal-title":"Biol. Pharm. Bull."},{"issue":"6","key":"10.1016\/j.ejps.2018.01.032_bb0110","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1248\/bpb.b12-01076","article-title":"In vitro evaluation of the ciliary beat frequency of the rat nasal epithelium using a high-speed digital imaging system","volume":"36","author":"Inoue","year":"2013","journal-title":"Biol. Pharm. Bull."},{"issue":"Suppl. 7","key":"10.1016\/j.ejps.2018.01.032_bb0115","first-page":"108","article-title":"Ciliary movement following various concentrations of different anticholinergic and adrenergic bronchodilator solutions in animals","volume":"51","author":"Iravani","year":"1975","journal-title":"Postgrad. Med. J."},{"key":"10.1016\/j.ejps.2018.01.032_bb0120","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1476-5381.1994.tb13100.x","article-title":"Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin","volume":"112","author":"Kanthakumar","year":"1994","journal-title":"Br. J. Pharmacol."},{"issue":"3","key":"10.1016\/j.ejps.2018.01.032_bb0125","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3109\/10717544.2014.920431","article-title":"Nasal-nanotechnology: revolution for efficient therapeutics delivery","volume":"23","author":"Kumar","year":"2016","journal-title":"Drug Deliv."},{"key":"10.1016\/j.ejps.2018.01.032_bb0130","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00418-008-0455-2","article-title":"The epithelial cholinergic system of the airways","volume":"130","author":"Kummer","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0135","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000194607","article-title":"Acute effect of inhaled salbutamol on mucociliary clearance in health and chronic bronchitis","volume":"45","author":"Lafortuna","year":"1984","journal-title":"Respiration"},{"key":"10.1016\/j.ejps.2018.01.032_bb0140","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1164\/ajrccm\/140.1.132","article-title":"Role of mucus and cilia in nasal mucociliary clearance in healthy subjects","volume":"140","author":"Liote","year":"1989","journal-title":"Am. Rev. Respir. Dis."},{"key":"10.1016\/j.ejps.2018.01.032_bb0145","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0014-2999(85)90793-9","article-title":"The effect of isoprenaline on the ciliary activity of an in vitro preparation of rat trachea","volume":"112","author":"Lopez-Vidriero","year":"1985","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0150","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0034-5687(94)00080-J","article-title":"Rheological determinants of mucociliary transport in the nose of the rat","volume":"99","author":"Macchione","year":"1995","journal-title":"Respir. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0155","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ijpharm.2007.01.029","article-title":"Effect of preservatives on ciliary beat frequency in human nasal epithelial cell culture: single versus multiple exposure","volume":"338","author":"Mallants","year":"2007","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2018.01.032_bb0160","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1365-2273.1995.tb01595.x","article-title":"Measurement of nasal mucociliary transport rates on the isolated human inferior turbinate","volume":"20","author":"Mason","year":"1995","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"10.1016\/j.ejps.2018.01.032_bb0165","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0169-409X(97)00059-8","article-title":"Nasal mucociliary clearance as factor in nasal drug delivery","volume":"29","author":"Merkus","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejps.2018.01.032_bb0170","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1136\/thx.41.4.301","article-title":"Effect of selective and non-selective beta blockade on pulmonary function and tracheobronchial mucociliary clearance in healthy subjects","volume":"41","author":"Pavia","year":"1986","journal-title":"Thorax"},{"key":"10.1016\/j.ejps.2018.01.032_bb0175","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1152\/jappl.1990.69.2.424","article-title":"Mucus-depleted frog palate as a model for the study of mucociliary clearance","volume":"69","author":"Rubin","year":"1990","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0180","doi-asserted-by":"crossref","first-page":"S275","DOI":"10.1067\/mai.2002.129412","article-title":"Effects of beta-agonists on airway epithelial cells","volume":"110","author":"Salathe","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0185","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev.physiol.69.040705.141253","article-title":"Regulation of mammalian ciliary beating","volume":"69","author":"Salathe","year":"2007","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0190","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/jat.2550150410","article-title":"Nasal mucociliary clearance in rats: differences with sex and phase of the oestrous cycle","volume":"15","author":"Saldiva","year":"1995","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0195","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1164\/ajrccm\/139.2.432","article-title":"Mechanosensitive and beta-adrenergic control of the ciliary beat frequency of mammalian respiratory tract cells in culture","volume":"139","author":"Sanderson","year":"1989","journal-title":"Am. J. Respir. Dis."},{"key":"10.1016\/j.ejps.2018.01.032_bb0200","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1023\/A:1015830907632","article-title":"The nasal mucociliary clearance: relevance to nasal drug delivery","volume":"8","author":"Schipper","year":"1991","journal-title":"Pharm. Res."},{"issue":"32","key":"10.1016\/j.ejps.2018.01.032_bb0205","doi-asserted-by":"crossref","first-page":"E40","DOI":"10.1208\/pt0802032","article-title":"Rheological characterization of neutral and anionic polysaccharides with reduced mucociliary transport rates","volume":"8","author":"Shah","year":"2007","journal-title":"AAPS PharmSciTech"},{"issue":"33","key":"10.1016\/j.ejps.2018.01.032_bb0210","doi-asserted-by":"crossref","first-page":"E48","DOI":"10.1208\/pt0802033","article-title":"Formulating gels for decreased mucociliary transport using rheologic properties: polyacrylic acids","volume":"8","author":"Shah","year":"2007","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.ejps.2018.01.032_bb0215","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1113\/jphysiol.2003.056481","article-title":"Beta 2-adrenergic regulation of ciliary beat frequency in rat bronchiolar epithelium: potentiation by isosmotic cell shrinkage","volume":"554","author":"Shiima-Kinoshita","year":"2004","journal-title":"J. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0220","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v21.i3.20","article-title":"Mucosal drug delivery: membranes, methodologies, and applications","volume":"21","author":"Song","year":"2004","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"10.1016\/j.ejps.2018.01.032_bb0225","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1517\/14712598.1.1.49","article-title":"Prodrugs in nasal drug delivery","volume":"1","author":"Tirucherai","year":"2001","journal-title":"Expert. Opin. Biol. Ther."},{"key":"10.1016\/j.ejps.2018.01.032_bb0230","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/0014-2999(90)90050-G","article-title":"Biochemical and autoradiographic analysis of beta-adrenoceptors in rat nasal mucosa","volume":"182","author":"Van Megen","year":"1990","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0235","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1164\/ajrccm.154.6.8970383","article-title":"Mucociliary clearance in the airways","volume":"154","author":"Wanner","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.ejps.2018.01.032_bb0240","first-page":"L827","article-title":"Regulation of ciliary beat frequency by both PKA and PKG in bovine airway epithelial cells","volume":"275","author":"Wyatt","year":"1998","journal-title":"Am. J. Phys."},{"key":"10.1016\/j.ejps.2018.01.032_bb0245","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1085\/jgp.20028519","article-title":"The mechanism of ciliary stimulation by acetylcholine: roles of calcium, PKA, and PKG","volume":"119","author":"Zagoory","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0250","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ejps.2007.08.006","article-title":"Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties","volume":"32","author":"Zaki","year":"2007","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejps.2018.01.032_bb0255","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1177\/000348940811700211","article-title":"Effect of oxymetazoline on healthy human nasal ciliary beat frequency measured with high-speed digital microscopy and mucociliary transport time","volume":"177","author":"Zhang","year":"2008","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"10.1016\/j.ejps.2018.01.032_bb0260","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0378-5173(96)04441-9","article-title":"Intranasal mucociliary clearance of putative bioadhesive polymer gels","volume":"135","author":"Zhou","year":"1996","journal-title":"Int. J. Pharm."}],"container-title":["European Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098718300393?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098718300393?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T19:32:53Z","timestamp":1589830373000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0928098718300393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":52,"alternative-id":["S0928098718300393"],"URL":"https:\/\/doi.org\/10.1016\/j.ejps.2018.01.032","relation":{},"ISSN":["0928-0987"],"issn-type":[{"value":"0928-0987","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The relationship between in vivo nasal drug clearance and in vitro nasal mucociliary clearance: Application to the prediction of nasal drug absorption","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejps.2018.01.032","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}