Absorption enhancement of adefovir dipivoxil by incorporating MCT and ethyl oleate complex oil phase in emulsion
文献类型：期刊论文
| 作者 | Li, Ping; Yu, Hong-zhen; Zhang, Xin-xin ; Gan, Li; Zhu, Chun-liu; Gan, Yong
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2010-07 |
| 卷号 | 31期号:7页码:881-888 |
| 关键词 | adefovir dipivoxil intestinal metabolism emulsions permeability oral absorption |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2010.60 |
| 文献子类 | Article |
| 英文摘要 | Aim: To improve the oral absorption of adefovir dipivoxil (ADV) by employing MCT and the esterase inhibitor ethyl oleate (EO) as a complex oil phase in emulsion. Methods: EO was used as the esterase inhibitor, and its inhibitory effect on esterase activity was assessed in rat intestinal homogenates. ADV emulsions with or without EO were prepared. The emulsions' protective effect against intestinal metabolism was evaluated in rat luminal contents, ex vivo, as well as in vivo. Results: The IC(50) of EO in intestinal mucosal homogenates was 2.2 mg/mL. The emulsions exhibited significant protective effects in rat luminal contents compared to a simple suspension (98.7%, 96.3%, 95.7% vs 74.7%, P<0.01). The permeability calculated from the emulsion containing EO was significantly different (11.4x10(-6) vs 7.4/8.0x10(-6), P<0.05) from the simple suspension or the emulsion without EO in an ex vivo assay. A bioavailability study in vivo revealed that emulsions containing both EO and MCT as a complex oil phase demonstrated 1.6- and 1.5-fold enhancements in area under the curve (AUC(0-12)) values (5358 vs 3386/3618, P<0.05), respectively, when compared with emulsions containing EO or MCT as a single oil phase. Conclusion: Heterotic lipid formulations (emulsions) with an esterase inhibitor (ie, EO) may be useful in protecting ester prodrugs from intestinal metabolism and increasing their oral bioavailability. |
| WOS关键词 | WATER-SOLUBLE DRUGS ; PRODRUG TENOFOVIR DISOPROXIL ; LIPID-BASED FORMULATIONS ; IN-VITRO LIPOLYSIS ; FATTY-ACID ETHYL ; INTESTINAL METABOLISM ; ORAL ABSORPTION ; SELECTIVE-INHIBITION ; LIPOPHILIC DRUGS ; ESTER PRODRUGS |
| 资助项目 | National Natural Sciences Foundation of China[30701054] ; National Science & Technology Major Project's Key New Drug Creation and Manufacturing Program[2009ZX09301-001] ; National Basic Research Program of China[2009CB930300] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3893626 |
| WOS记录号 | WOS:000279538400016 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278843]  |
| 专题 | 药物制剂研究中心 成果转移转化处 |
| 通讯作者 | Gan, Yong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Ping,Yu, Hong-zhen,Zhang, Xin-xin,et al. Absorption enhancement of adefovir dipivoxil by incorporating MCT and ethyl oleate complex oil phase in emulsion[J]. ACTA PHARMACOLOGICA SINICA,2010,31(7):881-888. |
| APA | Li, Ping,Yu, Hong-zhen,Zhang, Xin-xin,Gan, Li,Zhu, Chun-liu,&Gan, Yong.(2010).Absorption enhancement of adefovir dipivoxil by incorporating MCT and ethyl oleate complex oil phase in emulsion.ACTA PHARMACOLOGICA SINICA,31(7),881-888. |
| MLA | Li, Ping,et al."Absorption enhancement of adefovir dipivoxil by incorporating MCT and ethyl oleate complex oil phase in emulsion".ACTA PHARMACOLOGICA SINICA 31.7(2010):881-888. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。