{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:20:17Z","timestamp":1787653217397,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Leuprolide acetate is a potent agonist of luteinizing hormone-releasing hormone that has been licensed to treat prostate cancer. The microsphere formulation of leuprolide acetate called Beiyi\u00ae, developed in China, has shown favorable pharmacokinetics, pharmacodynamics and safety similar to those of the reference drug Enantone\u00ae in healthy individuals. The present study examined whether the two formulations are bioequivalent in men with prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter, open-label study randomized 120 Chinese men with prostate cancer 1:1 to receive a single subcutaneous injection of Beiyi\u00ae or Enantone\u00ae (3.75\u00a0mg). The two groups were compared in terms of pharmacokinetics and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The ratio of the geometric means of the maximum serum concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) of Beiyi\u00ae and Enantone\u00ae was 98.34% (91.88%\u2013105.25%); the ratio of the geometric means of the concentration-time curve from 7 to 28\u00a0days (AUC\n                      <jats:sub>7-28<\/jats:sub>\n                      ) was 100.52% (88.17%\u2013114.60%); and the ratio of the geometric means of the concentration-time curve from 0 to 28\u00a0days (AUC\n                      <jats:sub>0-28<\/jats:sub>\n                      ) was 109.07% (98.54%\u2013120.73%). The three 90% confidence intervals fell within the range of 80.00%\u2013125.00%, indicating similar pharmacokinetics. The two drugs showed similar safety profiles, with no treatment-emergent adverse events leading to withdrawal or death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The two formulations of leuprolide acetate microspheres Beiyi\u00ae and Enantone\u00ae show similar pharmacokinetics and safety in Chinese men with prostate cancer. These results support the further clinical development of Beiyi\u00ae as a generic formulation of Enantone\u00ae.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      CTR20222654 on\n                      <jats:ext-link>http:\/\/www.chinadrugtrials.org.cn\/index.html<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1873100","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:35:44Z","timestamp":1787650544000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Beiyi\u00ae and its reference product Enantone\u00ae as agonists of luteinizing hormone-releasing hormone against prostate cancer: a multicenter, randomized single-dose study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuyao","family":"Yi","sequence":"first","affiliation":[{"name":"Clinical Trial Center, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongsen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Harbin Medical University Cancer Hospital","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruigang","family":"Hou","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianlian","family":"Fan","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Deyang People\u2019s Hospital","place":["Deyang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Yu","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Second Affiliated Hospital of Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fang","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Harbin Medical University Cancer Hospital","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, Second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinghong","family":"You","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, Deyang People\u2019s Hospital","place":["Deyang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Lu","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongbing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, Second Affiliated Hospital of Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Urology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Feng","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.2147\/tcrm.s6863","article-title":"Leuprorelin depot injection: patient considerations in the management of prostatic cancer","volume":"4","author":"Abouelfadel","year":"2008","journal-title":"Ther. Clin. Risk Manag."},{"key":"B2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.annder.2010.08.025","article-title":"Granulomes induits par des injections de leupror\u00e9line ac\u00e9tate (Enantone \u00ae)","volume":"138","author":"Bruneu-Avierinos","year":"2011","journal-title":"Ann. Dermatol Venereol."},{"key":"B3","unstructured":"Technical guidelines for the study of human bioequivalence of chemical drug generics using pharmacokinetic parameters as evaluation indicators\n          \n          \n          2016"},{"key":"B4","first-page":"1366","article-title":"Study on ADR signal detection of leuprolide and goserelin based on the US FAERS database","volume":"39","author":"Chen","year":"2020","journal-title":"Her. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.eururo.2016.08.002","article-title":"EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer","volume":"71","author":"Cornford","year":"2017","journal-title":"Eur. Urol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1590\/S1677-5538.IBJU.2019.0212","article-title":"Efficacy of Leuprorelide acetate (Eligard\u00ae) in daily practice in Brazil: a retrospective study with depot formulations in patients with prostate cancer","volume":"46","author":"de Freitas","year":"2020","journal-title":"Int. Braz J. Urol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4103\/aja.aja_22_20","article-title":"Androgen deprivation therapy and side effects: are GnRH antagonists safer? are GnRH antagonists safer?","volume":"23","author":"Freedland","year":"2021","journal-title":"Asian J. Androl."},{"key":"B8","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3390\/cells13090749","article-title":"CD4+ T-Cell senescence in neurodegenerative disease: pathogenesis and potential therapeutic targets","volume":"13","author":"Gao","year":"2024","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/1756287212471096","article-title":"Clinical development of two innovative pharmaceutical forms of leuprorelin acetate","volume":"5","author":"Geiges","year":"2013","journal-title":"Ther. Adv. Urol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jncc.2024.01.006","article-title":"Cancer incidence and mortality in China, 2022","volume":"4","author":"Han","year":"2024","journal-title":"J. Natl. Cancer Cent."},{"key":"B11","doi-asserted-by":"publisher","first-page":"946505","DOI":"10.3389\/fphar.2022.946505","article-title":"A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and enantone\u00ae 3.75 mg in healthy male subjects","volume":"13","author":"Hu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1056\/NEJMoa1212299","article-title":"Intermittent versus continuous androgen deprivation in prostate cancer","volume":"368","author":"Hussain","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00228-025-03811-z","article-title":"Clinical pharmacology-how it shapes the drug development journey","volume":"81","author":"Kruse","year":"2025","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e000040","DOI":"10.1136\/esmoopen-2016-000040","article-title":"International survey of androgen deprivation therapy (ADT) for non-metastatic prostate cancer in 19 countries","volume":"1","author":"Liede","year":"2016","journal-title":"ESMO Open"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.1158\/1078-0432.CCR-10-2815","article-title":"Targeting continued androgen receptor signaling in prostate cancer","volume":"17","author":"Massard","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"430","DOI":"10.5505\/tjo.2020.2449","article-title":"Cost-effectiveness analysis of leuprorelin acetate atrigel in the treatment of prostate cancer","volume":"35","author":"\u00d6zyi\u011fit","year":"2020","journal-title":"Turk J. Oncol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3390\/pharmaceutics16050598","article-title":"A two-way proposal for the determination of bioequivalence for narrow therapeutic index drugs in the European Union","volume":"16","author":"Paixao","year":"2024","journal-title":"Pharmaceutics"},{"key":"B18","first-page":"S3","article-title":"Androgen deprivation therapy in the treatment of advanced prostate cancer","volume":"9","author":"Perlmutter","year":"2007","journal-title":"Rev. Urol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"930","DOI":"10.2165\/00003495-199448060-00008","article-title":"Leuprorelin: a review of its pharmacology and therapeutic use in prostatic cancer, endometriosis and other sex hormone-related disorders","volume":"48","author":"Plosker","year":"1994","journal-title":"Drugs"},{"key":"B20","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.clinthera.2019.01.004","article-title":"A new sustained-release, 3-month leuprolide acetate formulation achieves and maintains castrate concentrations of testosterone in patients with prostate cancer","volume":"41","author":"Shore","year":"2019","journal-title":"Clin. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"B22","doi-asserted-by":"publisher","first-page":"240108","DOI":"10.1155\/2013\/240108","article-title":"Adverse effects of androgen deprivation therapy for prostate cancer: prevention and management","volume":"2013","author":"Sountoulides","year":"2013","journal-title":"ISRN Urol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1093\/jjco\/hyv149","article-title":"Efficacy and safety of leuprorelin acetate 6-month depot in prostate cancer patients: a Phase III, randomized, open-label, parallel-group, comparative study in Japan","volume":"45","author":"Suzuki","year":"2015","journal-title":"Jpn. J. Clin. Oncol."},{"key":"B24","volume-title":"Enantone\u00ae (Leuprorelin Acetate Microspheres for Injection) Package Insert","year":"2024"},{"key":"B25","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1111\/bju.14980","article-title":"United in Fight against prOstate cancer (UFO) registry: first results from a large, multi-centre, prospective, longitudinal cohort study of advanced prostate cancer in Asia: asian UFO registry of advanced prostate cancer","volume":"125","author":"Uemura","year":"2020","journal-title":"BJU Int."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1517\/13543784.16.11.1851","article-title":"Leuprolide acetate: a drug of diverse clinical applications","volume":"16","author":"Wilson","year":"2007","journal-title":"Expert Opin. Investig. Drugs"},{"key":"B27","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s12916-026-04833-9","article-title":"Targeting immunosenescence in lung diseases: mechanistic insights and clinical interventions","volume":"24","author":"Zhang","year":"2026","journal-title":"BMC Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1080\/17425255.2021.1948534","article-title":"Pharmacokinetic and pharmacodynamic evaluation of the new prolonged-release leuprorelin acetate microspheres for injection compared with enantone\u00ae in healthy Chinese male volunteers","volume":"17","author":"Zhou","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1873100\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:35:45Z","timestamp":1787650545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1873100\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":28,"alternative-id":["10.3389\/fphar.2026.1873100"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1873100","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"article-number":"1873100"}}