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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
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
2012-10-01
DOI10.1002/jps.23236
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
WOS记录号WOS:000307966600039
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51109
专题北京大学药学院_药剂学系
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
推荐引用方式
GB/T 7714
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.
APA Li, Xingang,Li, Liang,Wang, Xipei,Ren, Yupeng,Zhou, Tianyan,&Lu, Wei.(2012).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.JOURNAL OF PHARMACEUTICAL SCIENCES,101(10),3946-3961.
MLA Li, Xingang,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".JOURNAL OF PHARMACEUTICAL SCIENCES 101.10(2012):3946-3961.
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