{"paper_id":"1a4f048d-00fa-4824-88bb-ec78ce080a5a","body_text":"Abstract\nIntroduction\nEndometriosis, a common and distressing gynecological condition, affects fertility and causes pain, is often managed with medications such as Elagolix. The present study aimed to construct a physiologically based pharmacokinetic (PBPK) model for elagolix to predict its pharmacokinetics in different populations, including those with special conditions, to enhance treatment strategies for endometriosis.\nMethods\nThe PBPK model was optimized using observational data based on the oral administration of elagolix in a healthy Chinese population under fasting conditions. Model accuracy was further verified by comparing the predicted postprandial elagolix concentration data for healthy Chinese individuals with observed data and by comparing these values with the predicted values in a US population model with renal injury or following multiple-dose administration.\nResults\nElagolix pharmacokinetic (PK) profiles in the Chinese and American populations exhibited no differences that were attributable to ethnicity. The model predicted in vivo PK in adolescents aged 14–18 years, revealing no clinically significant differences in the effects of elagolix between adolescents and adults. In addition, no predicted PK differences in individuals with overweight were observed. However, notable variations emerged in those classified as obesity class 2 and above compared to healthy individuals.\nConclusion\nOur study presents a novel PBPK model for elagolix in healthy Chinese women, addressing a clinical data gap for its use in adolescents and obese patients. By validating the model with real-world factors, including diet and renal impairment, we provide initial pharmacokinetic predictions for these populations, contributing to a more informed clinical approach.\nSimilar content being viewed by others\nChange history\n31 August 2024\nA Correction to this paper has been published: https://doi.org/10.1007/s40262-024-01415-x\nReferences\nSurrey ES, Soliman AM, Agarwal SK, Snabes MC, Diamond MP. Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis. Fertil Steril. 2019;112(2):298-304.e3.\nBulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, et al. Endometriosis. Endocr Rev. 2019;40(4):1048–79.\nDinsdale N, Nepomnaschy P, Crespi B. The evolutionary biology of endometriosis. Evol Med Public Health. 2021;9(1):174–91.\nDonnez J, Dolmans M-M. GnRH antagonists with or without add-back therapy: a new alternative in the management of endometriosis? 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Appreciation to the technical engineer Wang Yuxi from Shanghai PharmGO Company for the technical support provided.\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nFunding\nThis study was funded by Science and technology development plan of Jinan Health Commission (2024), Jinan Technology Development Program, China (Grant No. 202134049) and Shandong Province Medical and Health Technology Project (202313010781).\nConflict of interest\nXinghai Zhang, Xuanxuan Wang, Rui Li, Chenning Zhang, Jianmin Du, Hengli Zhao, and Qing Wen declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.\nAuthor contributions\nXinghai Zhang and Hengli Zhao wrote the manuscript. Xuanxuan Wang and Rui Li acquired, analyzed and interpreted the data. Xinghai Zhang, Jianmin Du and Chenning Zhang built the model. Qing Wen and Hengli Zhao designed the study. All authors read and approved the final manuscript.\nData Availability\nThe datasets generated during and/or analysed during the current study are available from the corresponding author (Qing Wen) on reasonable request.\nEthical Approval\nSome of the data in this study were derived from clinical trials conducted at our center. The clinical trial was reviewed and approved by the Ethics Committee of the Central Hospital Affiliated to Shandong First Medical University (Jinan, China).\nCode availability\nNot applicable.\nConsent to participate\nNot applicable.\nConsent for publication\nNot applicable.\nAdditional information\nThe original online version of this article was revised to include the co-corresponding author and the revised supplementary file.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nZhang, X., Wang, X., Li, R. et al. Development and Application of a Physiologically Based Pharmacokinetic Model for Elagolix in the Adult and Adolescent Population. Clin Pharmacokinet 63, 1357–1370 (2024). https://doi.org/10.1007/s40262-024-01402-2\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s40262-024-01402-2","source_license":"CC0","license_restricted":false}