Potential role of organic anion transporting polypeptide 1B1 (OATP1B1) in the selective hepatic uptake of hematoporphyrin monomethyl ether isomers
文献类型：期刊论文
| 作者 | Li, Xiu-li1; Guo, Zi-tao1; Wang, Ye-dong2; Chen, Xiao-yan1 ; Liu, Jia1; Zhong, Da-fang1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2015-02 |
| 卷号 | 36期号:2页码:268-280 |
| 关键词 | hematoporphyrin monomethyl ether photodynamic therapy OATP transporter hepatic uptake pharmacokinetics |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2014.104 |
| 文献子类 | Article |
| 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 OATP1B3 mediated a higher HMME-1 uptake. OATP1B1 exhibited a higher affinity for HMME-2 than for HMME-1 (the K-m values were 0.63 and 5.61 mu mol/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: OATP1B1 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. |
| WOS关键词 | DRUG-DRUG INTERACTION ; PHOTODYNAMIC THERAPY ; CYCLOSPORINE-A ; SLCO1B1 POLYMORPHISMS ; CATION TRANSPORTERS ; HEALTHY-VOLUNTEERS ; MAJOR DETERMINANT ; C SLC21A6 ; PHARMACOKINETICS ; INHIBITION |
| 资助项目 | National Natural Science Foundation of China[81173117] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5351059 |
| WOS记录号 | WOS:000349333700013 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276656]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zhong, Da-fang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet Res, Shanghai 201203, Peoples R China; 2.Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xiu-li,Guo, Zi-tao,Wang, Ye-dong,et al. Potential role of organic anion transporting polypeptide 1B1 (OATP1B1) in the selective hepatic uptake of hematoporphyrin monomethyl ether isomers[J]. ACTA PHARMACOLOGICA SINICA,2015,36(2):268-280. |
| APA | Li, Xiu-li,Guo, Zi-tao,Wang, Ye-dong,Chen, Xiao-yan,Liu, Jia,&Zhong, Da-fang.(2015).Potential role of organic anion transporting polypeptide 1B1 (OATP1B1) in the selective hepatic uptake of hematoporphyrin monomethyl ether isomers.ACTA PHARMACOLOGICA SINICA,36(2),268-280. |
| MLA | Li, Xiu-li,et al."Potential role of organic anion transporting polypeptide 1B1 (OATP1B1) in the selective hepatic uptake of hematoporphyrin monomethyl ether isomers".ACTA PHARMACOLOGICA SINICA 36.2(2015):268-280. |
入库方式： OAI收割
来源：上海药物研究所
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