{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:20:00Z","timestamp":1788153600540,"version":"build-2803163510"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1007\/s40262-024-01446-4","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:20:49Z","timestamp":1732098049000},"page":"1723-1734","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Population Pharmacokinetics of Ensitrelvir in Healthy Participants and Participants with SARS-CoV-2 Infection in the SCORPIO-SR Study"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-9980","authenticated-orcid":false,"given":"Toru","family":"Ishibashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9666-8678","authenticated-orcid":false,"given":"Ryosuke","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-4472","authenticated-orcid":false,"given":"Ryuji","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"issue":"9","key":"1446_CR1","doi-asserted-by":"publisher","first-page":"6499","DOI":"10.1021\/acs.jmedchem.2c00117","volume":"65","author":"Y Unoh","year":"2022","unstructured":"Unoh Y, Uehara S, Nakahara K, Nobori H, Yamatsu Y, Yamamoto S, et al. Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19. J Med Chem. 2022;65(9):6499\u2013512.","journal-title":"J Med Chem"},{"key":"1446_CR2","unstructured":"Xocova\u00ae (Ensitrelvir Fumaric Acid) tablets 125 mg approved in Japan for the treatment of SARS-CoV-2 infection, under the emergency regulatory approval system. https:\/\/www.shionogi.com\/global\/en\/news\/2022\/11\/e20221122.html. Accessed 15 Apr 2024."},{"key":"1446_CR3","unstructured":"Xocova\u00ae (Ensitrelvir Fumaric Acid) Tablets 125mg Approved in Japan for the Treatment of SARS-CoV-2 Infection. https:\/\/www.shionogi.com\/us\/en\/news\/2024\/03\/shionogi-announces-xocova-ensitrelvir-fumaric-acid-obtained-standard-approval-in-japan-for-the-treatment-of-sars-cov-2-infection.html. Accessed 15 Apr 2024."},{"key":"1446_CR4","doi-asserted-by":"publisher","first-page":"e00632","DOI":"10.1128\/aac.00632-22","volume":"66","author":"R Shimizu","year":"2022","unstructured":"Shimizu R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. Safety, tolerability, and pharmacokinetics of the novel antiviral agent ensitrelvir fumaric acid, a SARS-CoV-2 3CL protease inhibitor, in healthy adults. Antimicrob Agents Chemother. 2022;66:e00632-e722. https:\/\/doi.org\/10.1128\/aac.00632-22.","journal-title":"Antimicrob Agents Chemother"},{"key":"1446_CR5","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s40261-023-01309-z","volume":"43","author":"R Shimizu","year":"2023","unstructured":"Shimizu R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. A phase 1 study of ensitrelvir fumaric acid tablets evaluating the safety, pharmacokinetics and food effect in healthy adult populations. Clin Drug Investig. 2023;43:785\u201397. https:\/\/doi.org\/10.1007\/s40261-023-01309-z.","journal-title":"Clin Drug Investig"},{"key":"1446_CR6","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s40261-023-01265-8","volume":"43","author":"R Shimizu","year":"2023","unstructured":"Shimizu R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. Evaluation of the drug\u2013drug interaction potential of ensitrelvir fumaric acid with cytochrome P450 3A substrates in healthy Japanese adults. Clin Drug Investig. 2023;43:335\u201346. https:\/\/doi.org\/10.1007\/s40261-023-01265-8.","journal-title":"Clin Drug Investig"},{"issue":"8","key":"1446_CR7","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1002\/jcph.2247","volume":"63","author":"R Shimizu","year":"2023","unstructured":"Shimizu R, Matsuzaki T, Oka R, Sonoyama T, Fukuhara T, Kuwata A, et al. Evaluation of drug-drug interactions of ensitrelvir, a SARS-CoV-2 3CL protease inhibitor, with transporter substrates based on in vitro and clinical studies. J Clin Pharm. 2023;63(8):918\u201327. https:\/\/doi.org\/10.1002\/jcph.2247.","journal-title":"J Clin Pharm"},{"key":"1446_CR8","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.1093\/jac\/dkac257","volume":"77","author":"H Nobori","year":"2022","unstructured":"Nobori H, Fukao K, Kuroda T, Anan N, Tashima R, Nakashima M, et al. Efficacy of ensitrelvir against SARS-CoV-2 in a delayed-treatment mouse model. J Antimicrob Chemother. 2022;77:2984\u201391. https:\/\/doi.org\/10.1093\/jac\/dkac257.","journal-title":"J Antimicrob Chemother"},{"key":"1446_CR9","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1093\/cid\/ciac933","volume":"76","author":"H Mukae","year":"2023","unstructured":"Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Sakaguchi H, Sonoyama T, et al. Efficacy and safety of ensitrelvir in patients with mild-to-moderate coronavirus disease 2019: the phase 2b part of a randomized, placebo-controlled, phase 2\/3 study. Clin Infect Dis. 2023;76:1403\u201311. https:\/\/doi.org\/10.1093\/cid\/ciac933.","journal-title":"Clin Infect Dis"},{"key":"1446_CR10","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000033024","volume":"102","author":"H Yotsuyanagi","year":"2023","unstructured":"Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, Ichihashi G, et al. A phase 2\/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part). Medicine (Baltimore). 2023;102: e33024. https:\/\/doi.org\/10.1097\/md.0000000000033024.","journal-title":"Medicine (Baltimore)"},{"key":"1446_CR11","unstructured":"NONMEM User Guide 7.4 https:\/\/nonmem.iconplc.com\/nonmem741\/nm741.pdf. Accessed 15 Apr 2024."},{"key":"1446_CR12","unstructured":"SCM user guide of Perl-speaks NONMEM https:\/\/github.com\/UUPharmacometrics\/PsN\/releases\/download\/v5.3.1\/scm_userguide.pdf. Accessed 15 Apr 2024."},{"key":"1446_CR13","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1208\/s12248-011-9255-z","volume":"13","author":"M Bergstrand","year":"2011","unstructured":"Bergstrand M, Hooker AC, Wallin JE, Karlsson MO. Prediction corrected visual predictive checks for diagnosing nonlinear mixed effects models. AAPS J. 2011;13:143\u201351. https:\/\/doi.org\/10.1208\/s12248-011-9255-z.","journal-title":"AAPS J"},{"key":"1446_CR14","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/j.1552-4604.1997.tb04326.x","volume":"37","author":"EI Ette","year":"1997","unstructured":"Ette EI. Stability and performance of a population pharmacokinetic model. J Clin Pharmacol. 1997;37:486\u201395. https:\/\/doi.org\/10.1002\/j.1552-4604.1997.tb04326.x.","journal-title":"J Clin Pharmacol"},{"key":"1446_CR15","doi-asserted-by":"publisher","first-page":"e0069722","DOI":"10.1128\/aac.00697-22","volume":"66","author":"H Mukae","year":"2022","unstructured":"Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, et al. A randomized phase 2\/3 study of ensitrelvir, a novel oral SARS-CoV-2 3C-like protease inhibitor, in Japanese patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection: results of the phase 2a part. Antimicrob Agents Chemother. 2022;66:e0069722. https:\/\/doi.org\/10.1128\/aac.00697-22.","journal-title":"Antimicrob Agents Chemother"},{"key":"1446_CR16","doi-asserted-by":"publisher","first-page":"e2354991","DOI":"10.1001\/jamanetworkopen.2023.54991","volume":"7","author":"H Yotsuyanagi","year":"2024","unstructured":"Yotsuyanagi H, Ohmagari N, Doi Y, Yamato M, Nguyen HB, Cha BK, et al. Efficacy and safety of 5-day oral ensitrelvir for patients with mild to moderate COVID-19: the SCORPIO-SR randomized clinical trial. JAMA Netw Open. 2024;7:e2354991. https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.54991.","journal-title":"JAMA Netw Open"},{"key":"1446_CR17","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1186\/s12936-018-2466-3","volume":"17","author":"RM Hoglund","year":"2018","unstructured":"Hoglund RM, Ruengweerayut R, Na-Bangchang K. Population pharmacokinetics of mefloquine given as a 3-day artesunate\u2013mefloquine in patients with acute uncomplicated Plasmodium falciparum malaria in a multidrug-resistant area along the Thai-Myanmar border. Malar J. 2018;17:322. https:\/\/doi.org\/10.1186\/s12936-018-2466-3.","journal-title":"Malar J"},{"key":"1446_CR18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s10928-023-09856-w","volume":"50","author":"LF Amann","year":"2023","unstructured":"Amann LF, Wicha SG. Operational characteristics of full random effects modelling (\u2018frem\u2019) compared to stepwise covariate modelling (\u2018scm\u2019). J Pharmacokinet Pharmacodyn. 2023;50:315\u201326. https:\/\/doi.org\/10.1007\/s10928-023-09856-w.","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"1446_CR19","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1023\/a:1011970125687","volume":"15","author":"EN Jonsson","year":"1998","unstructured":"Jonsson EN, Karlsson MO. Automated covariate model building within NONMEM. Pharm Res. 1998;15:1463\u20138. https:\/\/doi.org\/10.1023\/a:1011970125687.","journal-title":"Pharm Res"},{"key":"1446_CR20","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.3390\/v15102052","volume":"15","author":"K Fukao","year":"2023","unstructured":"Fukao K, Nobori H, Kuroda T, Baba K, Matsumoto K, Tanaka Y, et al. Pharmacokinetic and pharmacodynamic analysis of the 3CL protease inhibitor ensitrelvir in a SARS-CoV-2 infection mouse model. Viruses. 2023;15:2052\u201365. https:\/\/doi.org\/10.3390\/v15102052.","journal-title":"Viruses"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-024-01446-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-024-01446-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-024-01446-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T14:11:01Z","timestamp":1734358261000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-024-01446-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":20,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["1446"],"URL":"https:\/\/doi.org\/10.1007\/s40262-024-01446-4","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]},"assertion":[{"value":"23 October 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was funded by Shionogi & Co., Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All authors are employees of Shionogi & Co., Ltd.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}},{"value":"The study was approved by Council for International Organizations of Medical Sciences International ethical guidelines and conducted in accordance with the Declaration of Helsinki and International Council for Harmonisation guidelines for good clinical practice. The SCORPIO-SR study (Phase 2\/3 study of S-217622) was conducted in Japan with the approval of\nthe ethics committee of a Japanese medical institution. Please see the Japanese registry site below.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All participants gave their written informed consent for participation in the study.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Shionogi & Co, Ltd is committed to disclosing the synopses and results of its clinical trials and sharing the clinical trial data with researchers on reasonable request. For further details, please refer to the websites of Shionogi & Co, Ltd () and Vivli ().","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"The code cannot be made public because it is a macro linked to our internal system.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"Conceptualization: TI, RS, RK. Methodology: TI, RS, RK. Formal analysis: TI, RS. Investigation: TI, RS, RK. Interpretation: TI, RS, RK. Writing: TI, RS, RK.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}