Enantioselective Plasma Protein Binding of Propafenone: Mechanism, Drug Interaction, and Species Difference
文献类型：期刊论文
| 作者 | Hong, Yanjun1; Tang, Yihong1,2; Zeng, Su1 |
| 刊名 | CHIRALITY
 |
| 出版日期 | 2009-07 |
| 卷号 | 21期号:7页码:692-698 |
| 关键词 | propafenone stereoselectivity plasma protein binding AGP HSA |
| ISSN号 | 0899-0042 |
| DOI | 10.1002/chir.20666 |
| 文献子类 | Article |
| 英文摘要 | The interaction of propafenone (PPF) enantiomers with human plasma, human serum albumin (HSA), alpha(1)-acid glycoprotein (AGP), as well as with plasma from rat, rabbit, and cow was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. The stronger binding of the S-PPF found in human plasma was due to AGP. Two classes of binding sites in AGP were identified: one with high-affinity and small binding capacity (K-1(S) = 7.65 x 10(6) M-1, n(1(S)) = 0.50; K-1(R) = 2.81 x 10(6) M-1, n(1(R)) = 0.46), which revealed stereoselectivity; the other with low-affinity and high-binding capacity (n(2(S))K(2(S)) = 9.95 x 10(3) M-1; n(2(R))K(2(R)) = 9.74 x 10(3) M-1). The binding to HSA was found to be weak and not enantioselective (nK(S) = 2.08 x 10(3) M-1, nK(R) = 2.05 x 10(3) M-1). The interaction between enantiomers observed in human plasma was confirmed as a competitive type interacting at the high-affinity site in AGP. The binding mode of both enantiomers with AGP was mainly hydrophobic bond. PPF enantiomers had higher-binding affinity for the F-S variant of human AGP. Drug-drug binding interaction studies showed that verapamil, diazepam, nifedipine, furosemide, nitrendipine, and nimodipine did not affect the binding of PPF enantiomers except quinidine and aprindine at the therapeutic concentration. Comparative studies indicated considerable species-dependent binding stereoselectivity between plasma of the four species investigated. Chirality 21:692-698, 2009. 02008 Wiley-Liss, Inc. |
| WOS关键词 | HUMAN ALPHA(1)-ACID GLYCOPROTEIN ; HUMAN ALPHA-1-ACID GLYCOPROTEIN ; GENETIC-VARIANTS ; LIQUID-CHROMATOGRAPHY ; ENANTIOMERS ; SERUM ; STEREOSELECTIVITY |
| 资助项目 | National Natural Science Foundation of China[30225047] ; Zhejiang Provincial Key Science and Technology Foundation of China[2005C13026] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000267459300008 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279197]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zeng, Su |
| 作者单位 | 1.Zhejiang Univ, Dept Pharmaceut Anal & Drug Metab, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hong, Yanjun,Tang, Yihong,Zeng, Su. Enantioselective Plasma Protein Binding of Propafenone: Mechanism, Drug Interaction, and Species Difference[J]. CHIRALITY,2009,21(7):692-698. |
| APA | Hong, Yanjun,Tang, Yihong,&Zeng, Su.(2009).Enantioselective Plasma Protein Binding of Propafenone: Mechanism, Drug Interaction, and Species Difference.CHIRALITY,21(7),692-698. |
| MLA | Hong, Yanjun,et al."Enantioselective Plasma Protein Binding of Propafenone: Mechanism, Drug Interaction, and Species Difference".CHIRALITY 21.7(2009):692-698. |
入库方式： OAI收割
来源：上海药物研究所
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