{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T11:18:32Z","timestamp":1761304712935,"version":"build-2065373602"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100002456","name":"Chonnam National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002456","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002562","name":"Sunchon National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002562","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1007\/s00210-025-04299-1","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T06:11:22Z","timestamp":1748499082000},"page":"16161-16179","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population modeling of pharmacokinetic variability of epinastine, a histamine H1 receptor antagonist, according to cytochrome P450 2D6 phenotypic polymorphisms"],"prefix":"10.1007","volume":"398","author":[{"given":"Ji-Hun","family":"Jang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Hyun","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"4299_CR1","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s000110050567","volume":"49","author":"U Amon","year":"2000","unstructured":"Amon U, Gibbs B, Buss G, Nitschke M (2000) In vitro investigations with the histamine H 1 receptor antagonist, epinastine (WAL 801 CL), on isolated human allergic effector cells. Inflamm Res 49:112\u2013116","journal-title":"Inflamm Res"},{"key":"4299_CR2","first-page":"373","volume":"7","author":"P Benly","year":"2015","unstructured":"Benly P (2015) Role of histamine in acute inflammation. J Pharm Sci Res 7:373","journal-title":"J Pharm Sci Res"},{"key":"4299_CR3","doi-asserted-by":"publisher","unstructured":"Borriello F, Iannone R, Marone G (2017) Histamine Release from Mast Cells and Basophils. In: Hattori Y, Seifert R (eds) Histamine and Histamine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 241. Springer, Cham. https:\/\/doi.org\/10.1007\/164_2017_18","DOI":"10.1007\/164_2017_18"},{"key":"4299_CR4","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S0014-2999(99)00375-1","volume":"374","author":"M Chachin","year":"1999","unstructured":"Chachin M, Katayama Y, Yamada M, Horio Y, Ohmura T, Kitagawa H, Uchida S, Kurachi Y (1999) Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel. Eur J Pharmacol 374:457\u2013460","journal-title":"Eur J Pharmacol"},{"key":"4299_CR5","unstructured":"DrugBank (n.d.) Epinastine. https:\/\/go.drugbank.com\/drugs\/DB00751. Accessed 28 Sept 2024"},{"key":"4299_CR6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S0923-1811(00)00110-9","volume":"25","author":"M Furue","year":"2001","unstructured":"Furue M, Terao H, Koga T (2001) Effects of cetirizine and epinastine on the skin response to histamine iontophoresis. J Dermatol Sci 25:59\u201363","journal-title":"J Dermatol Sci"},{"key":"4299_CR7","doi-asserted-by":"publisher","first-page":"534","DOI":"10.3109\/09540261.2013.825581","volume":"25","author":"A Gaedigk","year":"2013","unstructured":"Gaedigk A (2013) Complexities of CYP2D6 gene analysis and interpretation. Int Rev Psychiatry 25:534\u2013553","journal-title":"Int Rev Psychiatry"},{"key":"4299_CR8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/gim.2016.80","volume":"19","author":"A Gaedigk","year":"2017","unstructured":"Gaedigk A, Sangkuhl K, Whirl-Carrillo M, Klein T, Leeder JS (2017) Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med 19:69\u201376","journal-title":"Genet Med"},{"key":"4299_CR9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1159\/000024126","volume":"118","author":"JA Grant","year":"1999","unstructured":"Grant JA, Danielson L, Rihoux J-P, DeVos C (1999) A comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo in suppressing the cutaneous response to histamine. Int Arch Allergy Immunol 118:339\u2013340","journal-title":"Int Arch Allergy Immunol"},{"key":"4299_CR10","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1124\/dmd.32.5.519","volume":"32","author":"N Ishiguro","year":"2004","unstructured":"Ishiguro N, Nozawa T, Tsujihata A, Saito A, Kishimoto W, Yokoyama K, Yotsumoto T, Sakai K, Igarashi T, Tamai I (2004) Influx and efflux transport of H1-antagonist epinastine across the blood-brain barrier. Drug Metab Dispos 32:519\u2013524","journal-title":"Drug Metab Dispos"},{"key":"4299_CR11","first-page":"41","volume":"17","author":"I J\u00e1uregui","year":"2007","unstructured":"J\u00e1uregui I, Ferrer M, Montoro J, D\u00e1vila I, Bartra J, del Cuvillo A, Mullol J, Sastre J, Valero A (2007) Antihistamines in the treatment of chronic urticaria. J Investig Allergol Clin Immunol 17:41\u201352","journal-title":"J Investig Allergol Clin Immunol"},{"key":"4299_CR12","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3390\/molecules25010209","volume":"25","author":"S-H Jeong","year":"2020","unstructured":"Jeong S-H, Jang J-H, Cho H-Y, Lee Y-B (2020a) Pharmacokinetic comparison of epinastine using developed human plasma assays. Molecules 25:209","journal-title":"Molecules"},{"key":"4299_CR13","doi-asserted-by":"publisher","first-page":"e4848","DOI":"10.1002\/bmc.4848","volume":"34","author":"SH Jeong","year":"2020","unstructured":"Jeong SH, Jang JH, Cho HY, Lee YB (2020b) Simultaneous measurement of epinastine and its metabolite, 9, 13b-dehydroepinastine, in human plasma by a newly developed ultra-performance liquid chromatography\u2013tandem mass spectrometry and its application to pharmacokinetic studies. Biomed Chromatogr 34:e4848","journal-title":"Biomed Chromatogr"},{"key":"4299_CR14","doi-asserted-by":"publisher","first-page":"405","DOI":"10.4333\/KPS.2006.36.6.405","volume":"36","author":"H-A Kang","year":"2006","unstructured":"Kang H-A, Cho H-Y, Yoon H, Kim S-M, Kim D-H, Park S, Kim H-H, Lee Y-B (2006) Bioequivalence of S-napine tablet 10 mg to Alesion tablet (epinastine HCl 10 mg). J Pharm Investig 36:405\u2013411","journal-title":"J Pharm Investig"},{"key":"4299_CR15","first-page":"273","volume":"98","author":"W Kishimoto","year":"1997","unstructured":"Kishimoto W, Hiroi T, Sakai K, Funae Y, Igarashi T (1997) Metabolism of epinastine, a histamine H1 receptor antagonist, in human liver microsomes in comparison with that of terfenadine. Res Commun Mol Pathol Pharmacol 98:273\u2013292","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"4299_CR16","doi-asserted-by":"publisher","first-page":"734","DOI":"10.3390\/ph16050734","volume":"16","author":"J Neumann","year":"2023","unstructured":"Neumann J, Hofmann B, Kirchhefer U, Dhein S, Gergs U (2023) Function and role of histamine H1 receptor in the mammalian heart. Pharmaceuticals 16:734","journal-title":"Pharmaceuticals"},{"key":"4299_CR17","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1248\/bpb.24.790","volume":"24","author":"T Ogiso","year":"2001","unstructured":"Ogiso T, Kasutani M, Tanaka H, Iwaki M, Tanino T (2001) Pharmacokinetics of epinastine and a possible mechanism for double peaks in oral plasma concentration profiles. Biol Pharm Bull 24:790\u2013794","journal-title":"Biol Pharm Bull"},{"key":"4299_CR18","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1517\/17425250903117284","volume":"5","author":"S Pradhan","year":"2009","unstructured":"Pradhan S, Abhishek K, Mah F (2009) Epinastine: topical ophthalmic second generation antihistamine without significant systemic side effects. Expert Opin Drug Metab Toxicol 5:1135\u20131140","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"4299_CR19","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/humu.22936","volume":"37","author":"W Qiao","year":"2016","unstructured":"Qiao W, Yang Y, Sebra R, Mendiratta G, Gaedigk A, Desnick RJ, Scott SA (2016) Long-read single molecule real-time full gene sequencing of cytochrome P450\u20132D6. Hum Mutat 37:315\u2013323","journal-title":"Hum Mutat"},{"key":"4299_CR20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1365-2125.2005.2250","volume":"59","author":"A Sarashina","year":"2005","unstructured":"Sarashina A, Tatami S, Yamamura N, Tsuda Y, Igarashi T (2005) Population pharmacokinetics of epinastine, a histamine H1 receptor antagonist, in adults and children. Br J Clin Pharmacol 59:43\u201353","journal-title":"Br J Clin Pharmacol"},{"key":"4299_CR21","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1007\/s00228-006-0210-3","volume":"62","author":"J Saruwatari","year":"2006","unstructured":"Saruwatari J, Matsunaga M, Ikeda K, Nakao M, Oniki K, Seo T, Mihara S, Marubayashi T, Kamataki T, Nakagawa K (2006) Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. Eur J Clin Pharmacol 62:995\u20131001","journal-title":"Eur J Clin Pharmacol"},{"key":"4299_CR22","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1373\/clinchem.2004.043182","volume":"51","author":"E Soderback","year":"2005","unstructured":"Soderback E, Zackrisson A-L, Lindblom B, Alderborn A (2005) Determination of CYP2D6 gene copy number by pyrosequencing. Clin Chem 51:522\u2013531","journal-title":"Clin Chem"},{"key":"4299_CR23","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.3390\/genes11111295","volume":"11","author":"C Taylor","year":"2020","unstructured":"Taylor C, Crosby I, Yip V, Maguire P, Pirmohamed M, Turner RM (2020) A review of the important role of CYP2D6 in pharmacogenomics. Genes 11:1295","journal-title":"Genes"},{"key":"4299_CR24","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1046\/j.1365-2125.2002.01578.x","volume":"53","author":"SU Yasuda","year":"2002","unstructured":"Yasuda SU, Zannikos P, Young AE, Fried KM, Wainer IW, Woosley RL (2002) The roles of CYP2D6 and stereoselectivity in the clinical pharmacokinetics of chlorpheniramine. Br J Clin Pharmacol 53:519\u2013525","journal-title":"Br J Clin Pharmacol"},{"key":"4299_CR25","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1124\/dmd.105.005025","volume":"33","author":"OQ Yin","year":"2005","unstructured":"Yin OQ, Shi X, Tomlinson B, Chow MS (2005) Effect of CYP2D6* 10 allele on the pharmacokinetics of loratadine in Chinese subjects. Drug Metab Dispos 33:1283\u20131287","journal-title":"Drug Metab Dispos"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04299-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04299-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04299-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T11:13:22Z","timestamp":1761304402000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04299-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["4299"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04299-1","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"type":"print","value":"0028-1298"},{"type":"electronic","value":"1432-1912"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"assertion":[{"value":"1 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Clinical studies were conducted in accordance with the Rules of Good Clinical Practice and the revised Declaration of Helsinki for Biomedical Research with Human Subjects. All participants had no prior history of hypersensitivity or related reactions to corticosteroid drugs and were physically normal. In addition, healthy adults aged 19\u201355 years had no history of digestive, liver, kidney, cardiovascular, central nervous system, endocrine, or blood diseases, and were not taking any other drugs. To confirm physical health, all participants underwent a physical examination, clinical screening, complete blood count, urinalysis, and blood chemistry analyses prior to starting this clinical study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All participants provided written informed consent prior to starting the bioequivalence and PK studies.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All patient data were anonymized and participants were informed that the study results may be subject to publication and presentation at meetings.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The clinical study protocol used in this study was thoroughly reviewed and approved by the Institutional Review Board of the Institute of Bioequivalence and Bridging study, Chonnam National University, Gwangju, Republic of Korea. The bioequivalence study permit number was 050321\u201304.02.2005.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial registration"}},{"value":"The authors declare no competing interests.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}