potentialroleoforganicaniontransportingpolypeptide1b1oatp1b1intheselectivehepaticuptakeofhematoporphyrinmonomethyletherisomers

	potentialroleoforganicaniontransportingpolypeptide1b1oatp1b1intheselectivehepaticuptakeofhematoporphyrinmonomethyletherisomers
	Li Xiuli 1; Guo Zitao 1; Wang Yedong 2; Chen Xiaoyan 1; Liu Jia 1; Zhong Dafang 1
刊名	actapharmacologicasinica
	2015
卷号	000 期号:002 页码:268
关键词	血卟啉单甲醚离子转运异构体摄取肝脏多肽 HEK293 选择性吸收
ISSN号	1671-4083
英文摘要	Aim： Hematoporphyrin monomethyl ether （HMME）, which consists of equal amounts of isomers HMME-1 and HMME-2, is a novel porphyrin-related drug for photodynamic therapy. This study was aimed to investigate the uptake transporter-mediated selective uptake of HMME into the liver and to identify the major uptake transporter isoforms involved. Methods： Adult SD rats were intravenously injected with a single dose of HMME （5 mg/kg） with or without rifampicin （an inhibitor of organic anion transporting polypeptides OATP1B1 and OATP1B3, 25 mg/kg）. Blood samples were collected, and HMME concentrations were measured using LC-MS/MS. Rat hepatocytes, human hepatocytes and HEK293 cells expressing OATP1B1, OATP1B3, or OATP2B1 were used to investigate the uptake of HMME or individual isomers in vitro. Results Co-administration of rifampicin significantly increased the exposure of HMME isomers, and decreased the AUC ratio of HMME-1 to HMME-2 from 1.98 to 1.56. The uptake of HMME-2 into human hepatocytes and the HEK293 cells expressing OATP1B1 or OATP2B1 in vitro was 2-7 times greater than that of HMME-1, whereas OATPIB3 mediated a higher HMME-1 uptake. OATPIB1 exhibited a higher affinity for HMME-2 than for HMME-1 （the Km values were 0.63 and 5.61 μmol/L, respectively）, which were similar to those in human hepatocytes. By using telmisartan （a non-specific OATP inhibitor） and rifampicin, OATP2B1 was demonstrated to account for 〈20% of hepatic HMME uptake. Conclusion： OATPIB1 is the major transporter involved in the rapid hepatic uptake of HMME, and the greater uptake of HMME-2 by OATP1B1 may lead to a lower exposure of HMME-2 than HMME-1 in humans.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/286052]
专题	中国科学院上海药物研究所
作者单位	1.中国科学院上海药物研究所 2.苏州大学
推荐引用方式 GB/T 7714	Li Xiuli,Guo Zitao,Wang Yedong,et al. potentialroleoforganicaniontransportingpolypeptide1b1oatp1b1intheselectivehepaticuptakeofhematoporphyrinmonomethyletherisomers[J]. actapharmacologicasinica,2015,000(002):268.
APA	Li Xiuli,Guo Zitao,Wang Yedong,Chen Xiaoyan,Liu Jia,&Zhong Dafang.(2015).potentialroleoforganicaniontransportingpolypeptide1b1oatp1b1intheselectivehepaticuptakeofhematoporphyrinmonomethyletherisomers.actapharmacologicasinica,000(002),268.
MLA	Li Xiuli,et al."potentialroleoforganicaniontransportingpolypeptide1b1oatp1b1intheselectivehepaticuptakeofhematoporphyrinmonomethyletherisomers".actapharmacologicasinica 000.002(2015):268.