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Mechanistic study of herb-drug interactions between oseltamivir and TCM formulae. / Mechanistic study of herb-drug interactions between oseltamivir and traditional Chinese medicine formulae

Wang, Xiaoan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 145-166). / Abstracts in English and Chinese. / Table of Contents --- p.I / Acknowledgements --- p.VI / Publications --- p.VII / Abstract (in English) --- p.VIII / Abstract (in Chinese) --- p.X / List of Figures --- p.XII / List of Tables --- p.XVI / List of Abbreviations --- p.XVII / Chapter Chapter One. --- Introduction --- p.1 / Chapter 1.1 --- Overview of oseltamivir --- p.1 / Chapter 1.1.1 --- General description of oseltamivir --- p.1 / Chapter 1.1.2 --- Pharmacological activities of oseltamivir --- p.3 / Chapter 1.1.3 --- Pharmacokinetics of oseltamivir --- p.3 / Chapter 1.1.3.1 --- Absorption of oseltamivir --- p.4 / Chapter 1.1.3.2 --- Distribution of oseltamivir --- p.5 / Chapter 1.1.3.3 --- Metabolism of oseltamivir --- p.6 / Chapter 1.1.3.4 --- Elimination of oseltamivir --- p.8 / Chapter 1.1.4 --- Side effects and toxicities of oseltamivir --- p.9 / Chapter 1.2 --- Overview of Chinese medicine formulae CMF1 (Yinqiaosan and Sangjuyin) --- p.9 / Chapter 1.2.1 --- Background and clinical use of CMF1 --- p.9 / Chapter 1.2.2 --- Quality control of CMF1 by manufacturer --- p.11 / Chapter 1.2.3 --- Major active components of CMF1 --- p.12 / Chapter 1.3 --- Previous studies on herb-drug interactions between O and CMF1 --- p.18 / Chapter 1.4 --- Rationale of the current study --- p.19 / Chapter 1.5 --- objectives --- p.19 / Chapter Chapter Two. --- Identification and quantification of major marker compounds in Yinqiaosan and Sangiuyin products --- p.20 / Chapter 2.1 --- Introduction --- p.20 / Chapter 2.2 --- Materials and methods --- p.23 / Chapter 2.2.1 --- Chemicals --- p.23 / Chapter 2.2.2 --- Instruments --- p.24 / Chapter 2.2.3 --- Chromatographic conditions --- p.24 / Chapter 2.2.4 --- Preparation of standard solutions --- p.25 / Chapter 2.2.5 --- Calibration curves --- p.26 / Chapter 2.2.6 --- Validation of the assay method --- p.26 / Chapter 2.2.7 --- Sample preparations for Yinqiaosan and Sangjuyin products --- p.27 / Chapter 2.2.7.1 --- Sample extraction from Yinqiaosan or Sangjuyin granules --- p.27 / Chapter 2.2.7.2 --- Sample extraction from Yinqiaosan or Sangjuyin tablets --- p.27 / Chapter 2.2.7.3 --- Sample extraction recoveries --- p.27 / Chapter 2.3 --- Results and discussions --- p.28 / Chapter 2.3.1 --- Chromatography --- p.28 / Chapter 2.3.2 --- Linearity and sensitivity --- p.33 / Chapter 2.3.3 --- Accuracy and precision --- p.33 / Chapter 2.3.4 --- Stability --- p.36 / Chapter 2.3.5 --- Contents of identified active components in commercial available Yinqiaosan or Sangjuyin products and CMF1 --- p.36 / Chapter 2.3.6 --- Sample extraction recovery --- p.40 / Chapter 2.4 --- Conclusion --- p.43 / Chapter Chapter Three. --- Effect of CMF1/CMF1 components on the metabolism of oseltamivir and related mechanistic studies --- p.44 / Chapter 3.1 --- Introduction --- p.44 / Chapter 3.2 --- Materials and methods --- p.47 / Chapter 3.2.1 --- Materials --- p.47 / Chapter 3.2.2 --- "Verification of metabolism of O in rat GI tract, plasma and liver microsome" --- p.48 / Chapter 3.2.3 --- Inhibition of metabolism of O by CMFl/CMFl components --- p.49 / Chapter 3.2.3.1 --- In vitro inhibition of metabolism of O in rat plasma --- p.49 / Chapter 3.2.3.2 --- In vitro inhibition of metabolism of O in rat liver microsome (RLM) --- p.49 / Chapter 3.2.4 --- Mechanistic study of enzyme inhibition of O in recombinant human Carboxylesterase 1 (hCE 1) --- p.50 / Chapter 3.2.5 --- Sample preparation and LC/MS/MS analysis --- p.50 / Chapter 3.2.6 --- Data analyses --- p.52 / Chapter 3.3 --- Results --- p.53 / Chapter 3.3.1 --- "Verification of metabolism of O in rat GI tract, plasma and liver microsome" --- p.53 / Chapter 3.3.2 --- Inhibition of metabolism of O by CMF1/CMF1 components --- p.53 / Chapter 3.3.2.1 --- Enzyme inhibition of metabolism of O by CMFl/CMF1 components in rat plasma --- p.53 / Chapter 3.3.2.2 --- Enzyme inhibition of metabolism of O by CMF1/CMF1 components in rat liver microsome (RLM) --- p.58 / Chapter 3.3.2.3 --- Selection of potent enzyme inhibitor from CMF1 --- p.60 / Chapter 3.3.4. --- Mechanistic study of enzyme inhibition of O in recombinant human Carboxylesterase 1 (hCE 1) --- p.61 / Chapter 3.4 --- Discussions --- p.63 / Chapter 3.5 --- Conclusion --- p.74 / Chapter Chapter Four. --- Effect of CMFl/CMFl components on the absorption of oseltamivir and related mechanistic studies --- p.75 / Chapter 4.1 --- Introduction --- p.75 / Chapter 4.2 --- Materials and methods --- p.79 / Chapter 4.2.1 --- Materials --- p.79 / Chapter 4.2.2 --- PAMPA permeation model --- p.80 / Chapter 4.2.2.1 --- Permeation of O and OC in PAMPA --- p.80 / Chapter 4.2.2.2 --- Sample preparation and LC/MS/MS analysis --- p.81 / Chapter 4.2.2.3 --- Data analysis --- p.81 / Chapter 4.2.3 --- Absorption of O in presence of CMF/CMFl components in Caco-2 and MDCK cell monolayer models --- p.82 / Chapter 4.2.3.1 --- Cell culture --- p.82 / Chapter 4.2.3.2 --- Preparation of loading solutions to the cell models --- p.83 / Chapter 4.2.3.3 --- Stability of O in transport buffer --- p.84 / Chapter 4.2.3.4 --- Cytotoxicity tests of O and CMFl/CMFl components --- p.84 / Chapter 4.2.3.5 --- Transport study in Caco-2 and MDCK monolayer model --- p.85 / Chapter 4.2.3.6 --- Sample preparation and LC/MS/MS analysis --- p.86 / Chapter 4.2.3.7 --- Data analysis --- p.87 / Chapter 4.2.4 --- Absorption of O in presence of CMF 1 in rat in situ single pass intestinal perfusion model --- p.88 / Chapter 4.2.4.1 --- Preparation of perfusion solutions --- p.88 / Chapter 4.2.4.2 --- Stabilities of O and arctigenin in perfusate --- p.88 / Chapter 4.2.4.3 --- Rat in situ single pass intestinal perfusion of O in presence and absence of CMFl and relevant inhibitors --- p.89 / Chapter 4.2.4.4 --- Sample preparation and LC/MS/MS analysis --- p.90 / Chapter 4.2.4.5 --- Data analysis --- p.90 / Chapter 4.3 --- Resul ts --- p.91 / Chapter 4.3.1 --- Permeation of O and OC in PAMPA --- p.91 / Chapter 4.3.2 --- Absorption of O in presence of CMF/CMF1 components in Caco-2 and MDCK cell monolayer models --- p.92 / Chapter 4.3.2.1 --- Stabilities of O in transport buffer --- p.92 / Chapter 4.3.2.2 --- Cytotoxicity tests of O and CMF1/CMF1 components in transport buffer --- p.93 / Chapter 4.3.2.3 --- Proof of O as a substrate of P-gp by Caco-2 cell model --- p.95 / Chapter 4.3.2.4 --- Effect of CMF 1 on the absorption transport of o in Caco-2 cell mode --- p.98 / Chapter 4.3.2.5 --- Effect of CMF1 components on the absorption transport of o in Caco-2 cell model --- p.102 / Chapter 4.3.2.6 --- Effect of arctigenin on bi-directional transport of o in Caco- 2 cell model --- p.106 / Chapter 4.3.2.7 --- Proof of O as a substrate of P-gp by MDCK transfected cell lines --- p.108 / Chapter 4.3.2.8 --- Bi-directional transport of O in MDCK-MDR1 cell model --- p.111 / Chapter 4.3.2.9 --- Effect of CMF 1 on the absorption transport of O in MDCK-MDR1 cell model --- p.112 / Chapter 4.3.3 --- Absorption of O in presence of CMF1 in rat in situ single pass intestinal perfusion model --- p.113 / Chapter 4.3.3.1 --- Stabilities of O and arctigenin in the perfusion buffer --- p.113 / Chapter 4.3.3.2 --- Intestinal absorption of O in presence and absence of CMF1 in rat in situ intestinal perfusion model --- p.114 / Chapter 4.4 --- Discussions --- p.116 / Chapter 4.5 --- Conclusion --- p.124 / Chapter Chapter Five. --- Preliminary evaluation of antiviral activity of CMFl/CMFl components --- p.125 / Chapter 5.1 --- Introduction --- p.125 / Chapter 5.2 --- Materials and methods --- p.128 / Chapter 5.2.1 --- Materials and animals --- p.128 / Chapter 5.2.2 --- Animal treatment --- p.129 / Chapter 5.2.3 --- Plasma sample collection and preparation --- p.130 / Chapter 5.2.4 --- Evaluation of antiviral activities of CMFl/ CMFl components --- p.130 / Chapter 5.2.4.1 --- Plaque reduction assay --- p.131 / Chapter 5.2.4.2 --- Optimization of plasma sample dilution ratio --- p.131 / Chapter 5.2.5 --- Data analyses --- p.133 / Chapter 5.3 --- Results and discussions --- p.135 / Chapter 5.3.1 --- Ex vivo evaluation of antiviral activity of CMF1 --- p.135 / Chapter 5.3.2 --- In vitro evaluation of antiviral activity of CMF1 major marker compounds --- p.139 / Chapter 5.4 --- Conclusion --- p.141 / Chapter Chapter Six. --- Overall conclusion --- p.142 / References --- p.145

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_327217
Date January 2010
ContributorsWang, Xiaoan., Chinese University of Hong Kong Graduate School. Division of Pharmacy.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xix, 166 leaves : ill. (chiefly col.) ; 30 cm.
CoverageChina
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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