Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites

doi:10.1080/00498254.2016.1183060

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	Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites
	Zhou, Xin 1; Zhang, Fangrong 1; Chen, Chang 1; Guo, Zitao 3; Liu, Jia3 ; Yu, Jinghua 3; Xu, Yong 2; Zhong, Dafang3 ; Jiang, Hongliang 1
刊名	XENOBIOTICA
	2017
卷号	47 期号:3 页码:267-275
关键词	Curcumin drug-drug interaction OAT OATP rosuvastatin transporter
ISSN号	0049-8254
DOI	10.1080/00498254.2016.1183060
文献子类	Article
英文摘要	1. Plasma concentrations of curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS) significantly increased after Sprague-Dawley rats dealt with the Oatp inhibitor rifampicin, with the C-max ascending 2.9 and 6.7 times, and the AUC(0-infinity) ascending 4.4 and 10.8 times, respectively. When pretreated with the Oat inhibitor probenecid, the C-max increased 4.4 and 20 times, and the AUC(0-infinity) increased 3.2 and 13.9 times, respectively. The results suggested that COG and COS may be the substrates of Oatp and Oat. 2. The accumulation of curcumin significantly increased in organic anion transporting polypeptide (OATP)-and organic anion transporter (OAT)-transfected human embryonic kidney (HEK) 293 systems, which suggested that curcumin was a substrate of OATP1B1, OATP1B3, OATP2B1, OAT1, and OAT3; and COG was a substrate of OATP1B1, OATP1B3, and OAT3. 3. Inhibition study using rosuvastatin as the substrate in OATP1B1-and OATP1B3-transfected cells indicated that curcumin was an OATP1B1 and 1B3 inhibitor, with IC50 at 5.19 +/- 0.05 and 3.68 +/- 0.05 mu M, respectively; the data for COG were 1.04 +/- 0.01 and 1.08 +/- 0.02 mu M, respectively. COS was speculated to be an inhibitor of hepatic OATP1B1 as calculated using the ADMET Predictor. 4. COG and COS are substrates and inhibitors of OATP/Oatp. Co-administration of curcumin significantly increased rosuvastatin concentration in rat and dog plasma.
资助项目	China Postdoctoral Science Foundation[2014M552050]
WOS关键词	P-GLYCOPROTEIN ; UDP-GLUCURONOSYLTRANSFERASES ; HEPATIC-UPTAKE ; HUMAN PLASMA ; KETOCONAZOLE ; TRANSPORTERS ; DISPOSITION ; INHIBITION ; ABSORPTION ; CANCER
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	TAYLOR & FRANCIS LTD
WOS记录号	WOS:000393952200010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275736]
专题	上海药物代谢研究中心
通讯作者	Zhong, Dafang; Jiang, Hongliang
作者单位	1.Huazhong Univ Sci & Technol, Tongji Sch Pharm, Wuhan, Peoples R China; 2.Humanwell Healthcare Grp Co Ltd, Med Res Ctr, Wuhan, Hubei, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Zhou, Xin,Zhang, Fangrong,Chen, Chang,et al. Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites[J]. XENOBIOTICA,2017,47(3):267-275.
APA	Zhou, Xin.,Zhang, Fangrong.,Chen, Chang.,Guo, Zitao.,Liu, Jia.,...&Jiang, Hongliang.(2017).Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites.XENOBIOTICA,47(3),267-275.
MLA	Zhou, Xin,et al."Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites".XENOBIOTICA 47.3(2017):267-275.