The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats

doi:10.1016/j.cbi.2024.111228

科研成果详情

题名	The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats
作者	Lu, Guang-rong1; Wang, Rui-zhen 2; Zhao, Xin-yu 3; Xu, Jun-er 4; Huang, Cheng-ke3; Sun, Wei 3; Chen, Rui-jie3; Wang, Zhe 3
发表日期	2024-11-01
发表期刊	Chemico-Biological Interactions 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Sunitinib Pharmacokinetics Dexamethasone CYP3A enzyme Drug interaction
其他关键词	EXPRESSION ; INHIBITOR ; INDUCTION
摘要	Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC(0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC(0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.
资助项目	Science and Technology Project of Wenzhou [Y20240138]; Zhejiang Provincial Natural Science Foundation [ZCLTGD24H3101]; Medical and Health Science and Technology Project of Zhejiang Provincial Health Commission [2024KY1284]
出版者	ELSEVIER IRELAND LTD
ISSN	0009-2797
EISSN	1872-7786
卷号	403
DOI	10.1016/j.cbi.2024.111228
页数	6
WOS类目	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:001315379300001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39244184
SCOPUSEID	2-s2.0-85203457374
通讯作者地址	[Wang, Zhe]Wenzhou Med Univ, Affiliated Hosp & Yuying Childrens Hosp 2, Dept Pharm, Wenzhou, Zhejiang, Peoples R China.
Scopus学科分类	Toxicology
SCOPUS_ID	SCOPUS_ID:85203457374
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/218722
专题	第二临床医学院、附属第二医院、育英儿童医院阿尔伯塔学院第二临床医学院、附属第二医院、育英儿童医院_药学部
通讯作者	Wang, Zhe
作者单位	1.Wenzhou Med Univ, Affiliated Hosp & Yuying Childrens Hosp 2, Dept Gastroenterol, Wenzhou 325000, Zhejiang, Peoples R China; 2.Wenzhou Peoples Hosp, Dept Pharm, Wenzhou, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp & Yuying Childrens Hosp 2, Dept Pharm, Wenzhou, Zhejiang, Peoples R China; 4.Wenzhou Med Univ, Alberta Inst, Wenzhou, Zhejiang, Peoples R China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 药学部
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Lu, Guang-rong,Wang, Rui-zhen,Zhao, Xin-yu,et al. The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats[J]. Chemico-Biological Interactions,2024,403.
APA	Lu, Guang-rong., Wang, Rui-zhen., Zhao, Xin-yu., Xu, Jun-er., Huang, Cheng-ke., ... & Wang, Zhe. (2024). The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats. Chemico-Biological Interactions, 403.
MLA	Lu, Guang-rong,et al."The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats".Chemico-Biological Interactions 403(2024).