The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients
文献类型：期刊论文
| 作者 | Xie, Yuewu2; Zhang, Yifan1 ; Lin, Feifei1; Chen, Xiaoyue2; Xing, Jie2
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| 刊名 | INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
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| 出版日期 | 2024-07-01 |
| 卷号 | 64期号:1页码:11 |
| 关键词 | Malaria Drug metabolizing enzymes Piperaquine Clearance PBPK modelling |
| ISSN号 | 0924-8579 |
| DOI | 10.1016/j.ijantimicag.2024.107209 |
| 通讯作者 | Xing, Jie(xingjie@sdu.edu.cn) |
| 英文摘要 | Objectives: Malaria-induced alteration of physiological parameters and pharmacokinetic properties of antimalarial drugs may be clinically relevant. Whether and how malaria alters the disposition of piperaquine (PQ) was investigated in this study. Methods: The effect of malaria on drug metabolism-related enzymes and PQ pharmacokinetic profiles was studied in Plasmodium yoelii -infected mice in vitro/in vivo. Whether the malaria effect was clinically relevant for PQ was evaluated using a validated physiologically-based pharmacokinetic model with malaria-specific scalars obtained in mice. Results: The infection led to a higher blood-to-plasma partitioning ( Rbp ) for PQ, which was concentrationdependent and correlated to parasitemia. No significant change in plasma protein binding was found for PQ. Drug metabolism-related genes (CYPs/UDP-glucuronosyltransferase/nuclear receptor, except for CYP2a5) were downregulated in infected mice, especially at the acute phase. The plasma oral clearances (CL/F) of three probe substrates for CYP enzymes were significantly decreased (by >= 35.9%) in mice even with moderate infection. The validated physiologically-based pharmacokinetic model indicated that the hepatic clearance (CLH ) of PQ was the determinant of its simulated CL/F, which was predicted to slightly decrease (by <= 23.6%) in severely infected mice but not in malaria patients. The result fitted well with the plasma pharmacokinetics of PQ in infected mice and literature data on malaria patients. The blood clearance of PQ was much lower than its plasma clearance due to its high Rbp . Conclusions: The malaria-induced alteration of drug metabolism was substrate-dependent, and its impact on the disposition of PQ and maybe other long-acting aminoquinoline antimalarials was not expected to be clinically relevant. (c) 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those for text and data mining, AI training, and similar technologies. |
| WOS关键词 | HEPATIC BLOOD-FLOW ; FALCIPARUM-MALARIA ; POPULATION PHARMACOKINETICS ; UNCOMPLICATED FALCIPARUM ; COMBINATION THERAPIES ; SCALING FACTORS ; CLEARANCE ; MOUSE ; EXPRESSION ; DRUGS |
| 资助项目 | National Natural Science Foundation of China[82274005] ; National Natural Science Foundation of China[81773807] |
| WOS研究方向 | Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001257686900001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312041]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xing, Jie |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Shandong Univ, Sch Pharmaceut Sci, 44 West Wenhua Rd, Jinan 250012, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Yuewu,Zhang, Yifan,Lin, Feifei,et al. The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients[J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,2024,64(1):11. |
| APA | Xie, Yuewu,Zhang, Yifan,Lin, Feifei,Chen, Xiaoyue,&Xing, Jie.(2024).The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients.INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,64(1),11. |
| MLA | Xie, Yuewu,et al."The effect of malaria-induced alteration of metabolism on piperaquine disposition in Plasmodium yoelii infected mice and predicted in malaria patients".INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 64.1(2024):11. |
入库方式： OAI收割
来源：上海药物研究所
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