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学科主题: 药学
题名:
Application of model-based methods to characterize exenatide-loaded double-walled microspheres: In vivo release, pharmacokinetic/pharmacodynamic model, and in vitro and in vivo correlation
作者: Li, Xingang1; Li, Liang2; Wang, Xipei1; Ren, Yupeng1; Zhou, Tianyan1,2; Lu, Wei1,2
关键词: exenatide ; double-walled microspheres ; controlled release ; transit compartment model ; dose-response ; pharmacokinetic ; pharmacodynamic model ; simulation ; in vitro and in vivo correlation
刊名: JOURNAL OF PHARMACEUTICAL SCIENCES
发表日期: 2012-10-01
DOI: 10.1002/jps.23236
卷: 101, 期:10, 页:3946-3961
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy ; Chemistry
关键词[WOS]: TYPE-2 DIABETES-MELLITUS ; POLYMER MICROSPHERES ; POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES ; PLGA MICROSPHERES ; DOSAGE FORMS ; DEGRADATION ; RATS ; PHARMACOKINETICS ; PHARMACODYNAMICS ; EXENDIN-4
英文摘要:

The objective of this study was to characterize exenatide double-walled microspheres (DWMS) using model-based methods. Exenatide DWMS were prepared using oil-in-oil-in-water method, and physicochemical characterization and in vitro release and degradation of DWMS were evaluated. The pharmacokinetics (PK) and pharmacodynamics (PD) were investigated after subcutaneous injection to diabetic rats. Transit compartment model was used to describe the in vivo release of exenatide from DWMS successfully. On the basis of the insulinotropic effects of exenatide and hypoglycemic effects of insulin, PK/PD model was developed and nicely described the concentrationeffect relationship of exenatide. Moreover, on the basis of the transit compartment model, a simulation method was applied to predict in vivo release, and in vitro and in vivo correlation was established. In conclusion, DWMS was a promising vehicle for delivery of exenatide, and the proposed PK/PD model allowed a better understanding of the pharmacological properties of exenatide DWMS. Transit compartment model-based modeling and simulation methods provided more options for the description and prediction of the in vivo exenatide release from DWMS. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:39463961, 2012

语种: 英语
所属项目编号: 2009ZX09301-010
项目资助者: Ministry of Science and Technology of the People&prime ; s Republic of China (Peking University New Drug Research and Development Platform)
WOS记录号: WOS:000307966600039
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51109
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, Dept Pharmaceut, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Li, Xingang,Li, Liang,Wang, Xipei,et al. Application of model-based methods to characterize exenatide-loaded double-walled microspheres: In vivo release, pharmacokinetic/pharmacodynamic model, and in vitro and in vivo correlation[J]. JOURNAL OF PHARMACEUTICAL SCIENCES,2012,101(10):3946-3961.
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