| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-06-23 |
| タイトル |
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タイトル |
Population Pharmacokinetics-Pharmacodynamics and Exposure-Response of Ropeginterferon Alfa-2b in Chinese and Japanese Patients With Polycythemia Vera |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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言語 |
en |
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キーワード |
complete hematologic response (CHR) |
| キーワード |
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言語 |
en |
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キーワード |
exposure-response (E-R) |
| キーワード |
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言語 |
en |
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キーワード |
JAK2V617F allele burden |
| キーワード |
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言語 |
en |
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キーワード |
polycythemia vera (PV) |
| キーワード |
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言語 |
en |
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キーワード |
population pharmacokinetics-pharmacodynamics (PopPK-PD) |
| キーワード |
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言語 |
en |
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キーワード |
Ropeginterferon alfa-2b (ropeg) |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Qin, Albert
下田, 和哉
WEKO
7997
e-Rad_Researcher
90311844
| en |
Shimoda, Kazuya
University of Miyazaki
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| ja |
下田, 和哉
宮崎大学
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| ja-Kana |
シモダ, カズヤ
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Search repository
Suo, Shanshan
Fu, Rongfeng
| en |
Fu, Rongfeng
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Search repository
Kirito, Keita
Wu, Daoxiang
Liao, Jason
Chen, Haoqi
Wu, Lei
Su, Xia
Gao, Yucheng
Sato, Toshiaki
Li, Yaning
Zhang, Jingjing
Shen, Weihong
Wang, Wei
Zhang, Lei
| en |
Zhang, Lei
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
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Search repository
Jin, Jie
Komatsu, Norio
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Ropeginterferon alfa-2b (ropeg) represents a new-generation interferon-based therapy approved for polycythaemia vera (PV) treatment. This study aimed to elucidate its population pharmacokinetics-pharmacodynamics (PopPK-PD) and exposure-response (E-R) relationships. A PopPK model was developed using pooled data from four clinical studies, including two Phase I studies in healthy volunteers (n = 48) and two Phase II studies in Chinese or Japanese patients with PV (n = 78). Sequential modeling was used to analyze pharmacokinetics-pharmacodynamics (PK-PD) regarding hematological parameters, including hematocrit, platelet, and white blood cell counts. Hematological changes were simulated using fast- and slow-dose titration regimens. Individual exposure values were used to analyze the E-R relationships regarding complete hematologic response (CHR), driver mutation, JAK2V617F allele burden, and safety. In this study, we developed a target-mediated drug disposition model. Sigmoid indirect effects elucidated the PK-PD in terms of hematological changes. Simulations showed that the fast-titration regimen significantly accelerated hematocrit reduction. Logistic regression models showed that the probability of achieving CHR increased with exposure at Week 24 but not at Week 52. In contrast, JAK2V617F allele reductions correlated with exposure at both Weeks 24 and 52. Exposure-safety analysis revealed a manageable risk of adverse events associated with transaminase increases. This study established a robust framework for ropeg PK-PD, providing insights into its E-R relationships and disease-modifying action. |
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言語 |
en |
| bibliographic_information |
en : Pharmacology Research and Perspectives
巻 13,
号 3,
p. e70109,
発行日 2025-05-01
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| 出版者 |
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出版者 |
Wiley |
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言語 |
en |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
20521707 |
| item_10001_relation_14 |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1002/prp2.70109 |
| 権利 |
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権利情報 |
© 2025 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. |
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言語 |
en |
| 出版タイプ |
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出版タイプ |
VoR |
fulltext (968 KB)
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