An Examination of the Potential Effect of Lipids on the First-Pass Metabolism of the Lipophilic Drug Anethol Trithione
文献类型：期刊论文
| 作者 | Yu, Hong-Zhen; Han, Si-Fei; Li, Ping; Zhu, Chun-Liu ; Zhang, Xin-Xin; Gan, Li; Gan, Yong
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| 刊名 | JOURNAL OF PHARMACEUTICAL SCIENCES
 |
| 出版日期 | 2011-11 |
| 卷号 | 100期号:11页码:5048-5058 |
| 关键词 | anethol trithione medium chain triglycerides first-pass metabolism hepatic metabolism nonlinear pharmacokinetics dose proportionality drug metabolizing enzymes inhibition formulation lipids |
| ISSN号 | 0022-3549 |
| DOI | 10.1002/jps.22702 |
| 文献子类 | Article |
| 英文摘要 | In this study, an examination of the potential effect of lipids on the first-pass metabolism of anethol trithione (ATT) was investigated. ATT is metabolized rapidly and extensively in liver into 4-hydroxy-anethole trithione (ATX), which was confirmed using the rat intestinal perfusion with the mesenteric cannulation model. Male Sprague-Dawley rats were orally administered of the lipid-based formulations (prepared by medium chain triglycerides (MCT)), the cyclodextrin formulation and the suspension formulation, respectively. For 6.75 mg/kg groups, ATX/ATT area under the plasma concentration-time curve (AUC) ratio decreased by 87% and 76% after administration of the MCT-based formulations and the cyclodextrin formulation, when compared with the suspension formulation (p < 0.05), respectively; for 2.25 mg/kg groups, it decreased by 53% in the MCT group when compared with the cyclodextrin group (p < 0.05). The saturation of pre-system metabolism of ATT was observed after administration of the MCT-based formulations and the cyclodextrin formulation, likely as a result of enhanced absorption and therefore presentation of higher drug concentrations to liver, when compared with the suspension formulation. A trend toward lower systemic metabolite to parent ratios was evident after administration of the lipid formulations, when compared with the cyclodextrin formulation; however, this was not statistically significant. Further studies on the potential for lipids to inhibit hepatic metabolism are therefore warranted. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 5048-5058, 2011 |
| WOS关键词 | INTESTINAL LYMPHATIC TRANSPORT ; WATER-SOLUBLE DRUGS ; P-GLYCOPROTEIN ; BLOOD-FLOW ; PHARMACOKINETICS ; FORMULATIONS ; RAT ; ABSORPTION ; BIOAVAILABILITY ; HALOFANTRINE |
| 资助项目 | National Natural Sciences Foundation of China[30701054] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[07G603H071] ; National Basic Research Program of China[2009CB930300] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000296369700046 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278355]  |
| 专题 | 药物制剂研究中心 |
| 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 | Yu, Hong-Zhen,Han, Si-Fei,Li, Ping,et al. An Examination of the Potential Effect of Lipids on the First-Pass Metabolism of the Lipophilic Drug Anethol Trithione[J]. JOURNAL OF PHARMACEUTICAL SCIENCES,2011,100(11):5048-5058. |
| APA | Yu, Hong-Zhen.,Han, Si-Fei.,Li, Ping.,Zhu, Chun-Liu.,Zhang, Xin-Xin.,...&Gan, Yong.(2011).An Examination of the Potential Effect of Lipids on the First-Pass Metabolism of the Lipophilic Drug Anethol Trithione.JOURNAL OF PHARMACEUTICAL SCIENCES,100(11),5048-5058. |
| MLA | Yu, Hong-Zhen,et al."An Examination of the Potential Effect of Lipids on the First-Pass Metabolism of the Lipophilic Drug Anethol Trithione".JOURNAL OF PHARMACEUTICAL SCIENCES 100.11(2011):5048-5058. |
入库方式： OAI收割
来源：上海药物研究所
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