{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:40:51Z","timestamp":1792518051883,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Although approved doses in Japan have generally been lower than in Western countries, these differences have been diminished with global drug development. Studies evaluating dose differences between Japan and the United States (US) using post-2010 data are limited, and none have focused on the 2020s.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study characterized labeled dosage differences between Japan and the US for new molecular entities approved during 2020\n                      <jats:bold>\u2013<\/jats:bold>\n                      2025. Major differences were defined as a \u22652-fold difference in the maintenance or maximum dose; all others were classified as minor differences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 187 comparable drugs, 38 (20.3%) had dosage differences between Japan and the US: seven drugs (3.7%) showed major differences (three with higher doses in Japan and four with higher doses in the US), and 31 drugs (16.6%) showed minor differences. Common minor differences included initial-dose differences and body weight-based subgroup differences. Nervous system drugs showed the highest proportion of dosage differences (50.0%), followed by alimentary tract and metabolism (31.3%) and cardiovascular system drugs (22.2%). In contrast, dermatological (11.1%), antineoplastic (10.7%), and systemic anti-infective drugs (8.3%) showed lower proportions. No large differences were observed across assessed factors such as dosing types (fixed dose, per body weight) and administration routes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Approximately 20% of drugs approved in Japan during 2020\n                      <jats:bold>\u2013<\/jats:bold>\n                      2025 had dosage differences from those in the US. The proportion of drugs with dosage differences varied across therapeutic areas. Only 3.7% had major differences. These findings may reflect progress in the international harmonization of labeled drug dosages between Japan and the US.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43441-026-01064-1","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:02:37Z","timestamp":1792515757000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Labeled Dosages Between Japan and the United States for Drugs Approved in Japan from 2020 to 2025"],"prefix":"10.1007","author":[{"given":"Takashi","family":"Funatogawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"1064_CR1","unstructured":"Ministry of Health, Labour and Welfare. Basic Principles on Global Clinical Trials, September 28, 2007 https:\/\/www.pmda.go.jp\/files\/000153265.pdf"},{"key":"1064_CR2","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1177\/009286150904300313","volume":"43","author":"JL Saillot","year":"2009","unstructured":"Saillot JL, Paxion M. Industry efforts on simultaneous global development. Drug Inf J. 2009;43:339\u201347.","journal-title":"Drug Inf J"},{"key":"1064_CR3","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/clpt.2010.31","volume":"87","author":"FL Arnold","year":"2010","unstructured":"Arnold FL, Kusama M, Ono S. Exploring differences in drug doses between Japan and Western countries. Clin Pharmacol Ther. 2010;87:714\u201320.","journal-title":"Clin Pharmacol Ther"},{"key":"1064_CR4","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1177\/0091270010375958","volume":"51","author":"K Nakashima","year":"2011","unstructured":"Nakashima K, Narukawa M, Kanazu Y, et al. Differences between Japan and the United States in dosages of drugs recently approved in Japan. J Clin Pharmacol. 2011;51:549\u201360.","journal-title":"J Clin Pharmacol"},{"key":"1064_CR5","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1248\/bpb.b25-00030","volume":"48","author":"K Koyama","year":"2012","unstructured":"Koyama K, Abe Y, Kodama S, et al. Differences in approved doses and drug lag in drugs approved between 2012 and 2021: a comparison between Japan and the U.S. Biol Pharm Bull. 2012;48:1239\u201345.","journal-title":"Biol Pharm Bull"},{"key":"1064_CR6","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/clpt.2013.231","volume":"95","author":"FL Arnold","year":"2014","unstructured":"Arnold FL, Fukunaga S, Kusama M, et al. Assessment of factors associated with dose differences between Japan and the United States. Clin Pharmacol Ther. 2014;95:542\u20139.","journal-title":"Clin Pharmacol Ther"},{"key":"1064_CR7","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1177\/0091270008319794","volume":"48","author":"HJ Malinowski","year":"2008","unstructured":"Malinowski HJ, Westelinck A, Sato J, et al. Same drug, different dosing: differences in dosing for drugs approved in the United States, Europe, and Japan. J Clin Pharmacol. 2008;48:900\u20138.","journal-title":"J Clin Pharmacol"},{"key":"1064_CR8","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/clpt.2011.156","volume":"90","author":"K Nakashima","year":"2011","unstructured":"Nakashima K, Narukawa M, Takeuchi M. Approaches to Japanese dose evaluation in global drug development: factors that generate different dosages between Japan and the United States. Clin Pharmacol Ther. 2011;90:836\u201343.","journal-title":"Clin Pharmacol Ther"},{"key":"1064_CR9","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1177\/2160763X12455329","volume":"1","author":"Y Sugita","year":"2012","unstructured":"Sugita Y, Inoue E, Narukawa M. Impact of clinical response on different approved doses in Japan and the United States. Clin Pharmacol Drug Dev. 2012;1:158\u201369.","journal-title":"Clin Pharmacol Drug Dev"},{"key":"1064_CR10","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1177\/2168479018805432","volume":"53","author":"R Takayanagi","year":"2019","unstructured":"Takayanagi R, Endo Y, Kimura K, et al. Comparisons of usual dose of pharmaceutical products used in Japan and United States: can differences be explained by pharmacokinetics alone? Ther Innov Regul Sci. 2019;53:684\u201390.","journal-title":"Ther Innov Regul Sci"},{"key":"1064_CR11","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1177\/0091270010381500","volume":"51","author":"S Fukunaga","year":"2011","unstructured":"Fukunaga S, Kusama M, Arnold FL, et al. Ethnic differences in pharmacokinetics in new drug applications and approved doses in Japan. J Clin Pharmacol. 2011;51:1237\u201340.","journal-title":"J Clin Pharmacol"},{"key":"1064_CR12","unstructured":"International Conference on Harmonisation. Harmonised Tripartite Guideline: General Principles for Planning and Design of Multi-Regional Clinical Trials. ICH-E17. November 16, 2017 https:\/\/database.ich.org\/sites\/default\/files\/E17EWG_Step4_2017_1116.pdf"},{"key":"1064_CR13","unstructured":"Pharmaceutical and Medical Devices Agency, Japan. Regenerative Medical Products. https:\/\/www.pmda.go.jp\/english\/review-services\/reviews\/0003.html"},{"key":"1064_CR14","unstructured":"Pharmaceutical and Medical Devices Agency, Japan. Standards for Biological Raw Materials. March 31, 2026 https:\/\/www.pmda.go.jp\/files\/000280797.pdf"},{"key":"1064_CR15","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1002\/jcph.70065","volume":"65","author":"K Fukuhara","year":"2025","unstructured":"Fukuhara K, Tanetsugu Y, Wada S, et al. Evaluation of characteristics and ethnic sensitivity for FDA-approved drugs with racial and ethnic differences in pharmacokinetics, safety, and efficacy. J Clin Pharmacol. 2025;65:1381\u201391.","journal-title":"J Clin Pharmacol"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-01064-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-01064-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-01064-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:02:38Z","timestamp":1792515758000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-01064-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":15,"alternative-id":["1064"],"URL":"https:\/\/doi.org\/10.1007\/s43441-026-01064-1","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"30 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests for this work.","order":1,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}