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A study to investigate the mechanisms of the drug interactions between danshen and warfarin.

Wu Wai Ping. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 163-177). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgement --- p.vi / Table of Contents --- p.vii / Abbreviations --- p.x / Chapter Chapter 1 --- General introduction --- p.11 / Chapter 1.1 --- Introduction --- p.11 / Chapter 1.1.1 --- "Origin, processing and delivery form of TCM" --- p.11 / Chapter 1.1.2 --- Problems about the uses of TCM --- p.13 / Chapter 1.1.2.1 --- Quality control --- p.13 / Chapter 1.1.2.2 --- Efficacy --- p.14 / Chapter 1.1.2.3 --- Herb-drug interactions --- p.14 / Chapter 1.1.2.4 --- Authentication --- p.15 / Chapter 1.1.3 --- Commonly used Traditional Chinese Medicine --- p.15 / Chapter 1.2 --- Interactions between TCM and warfarin --- p.17 / Chapter 1.2.1 --- Danshen-warfarin interactions --- p.19 / Chapter 1.3 --- Danshen --- p.20 / Chapter 1.3.1 --- Chemical constituents --- p.20 / Chapter 1.3.2 --- Pharmacological effects of danshen --- p.24 / Chapter 1.3.2.1 --- Anti-oxidant effects --- p.24 / Chapter 1.3.2.2 --- Effects on liver fibrosis --- p.25 / Chapter 1.3.2.3 --- Effects on tumours --- p.26 / Chapter 1.3.2.4 --- Effects on cardiovascular system --- p.26 / Chapter 1.3.2.5 --- Effect on platelet aggregation --- p.27 / Chapter 1.4 --- Warfarin --- p.27 / Chapter 1.4.1 --- Pharmacology --- p.28 / Chapter 1.4.2 --- Pharmacokinetics --- p.30 / Chapter 1.4.3 --- Metabolism --- p.30 / Chapter 1.4.4 --- Warfarin-drug interactions --- p.32 / Chapter 1.4.4.1 --- Pharmacokinetic Interactions --- p.32 / Chapter 1.4.4.2 --- Pharmacodynamic interactions --- p.34 / Chapter 1.5 --- Aim of study --- p.35 / Chapter Chapter 2 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in rat liver microsomes --- p.36 / Chapter 2.1 --- Introduction --- p.36 / Chapter 2.2 --- Materials and methods --- p.39 / Chapter 2.2.1 --- Chemicals and reagents --- p.39 / Chapter 2.2.2 --- Animals --- p.39 / Chapter 2.2.3 --- Preparation of rat hepatic microsomes --- p.40 / Chapter 2.2.4 --- Protein assay --- p.40 / Chapter 2.2.5 --- Preparation of aqueous fraction and ethanolic fractions of danshen from danshen roots --- p.41 / Chapter 2.2.5.1 --- Aqueous extract of danshen --- p.41 / Chapter 2.2.5.2 --- Ethanolic extract of danshen --- p.42 / Chapter 2.2.6 --- Incubation condition for warfarin metabolism --- p.42 / Chapter 2.2.7 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in vitro --- p.43 / Chapter 2.2.8 --- Effects of danshen extract and some of its sctive ingredients on enzyme kinetics of warfarin metabolism in vitro --- p.44 / Chapter 2.2.9 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.45 / Chapter 2.2.10 --- Calibration curves and validation of the HPLC systems --- p.48 / Chapter 2.2.11 --- Data analysis --- p.52 / Chapter 2.3 --- Results --- p.53 / Chapter 2.3.1 --- Effects of danshen extract on warfarin metabolism --- p.53 / Chapter 2.3.2 --- Effects of aqueous extract of danshen on warfarin metabolism --- p.60 / Chapter 2.3.3 --- Effects of ethanolic extract of danshen on warfarin metabolism --- p.62 / Chapter 2.3.4 --- Effects of tanshinone I on warfarin metabolism --- p.64 / Chapter 2.3.5 --- Effects of tanshinone IIA on warfarin metabolism --- p.70 / Chapter 2.3.6 --- Effects of cryptotanshinone on warfarin metabolism --- p.76 / Chapter 2.3.7 --- IC20 of danshen extract and its components on warfarin metabolism --- p.82 / Chapter 2.4 --- Discussion --- p.84 / Chapter Chapter 3 --- Effects of danshen extract and some of its active ingredients on warfarin metabolism in human pooled liver microsomes and the human CYP2C9 isoform --- p.89 / Chapter 3.1 --- Introduction --- p.89 / Chapter 3.2 --- Materials and methods --- p.92 / Chapter 3.2.1 --- Chemicals and reagents --- p.92 / Chapter 3.2.2 --- Incubation conditions for warfarin metabolism --- p.92 / Chapter 3.2.3 --- Effects of danshen extract and its components on warfarin metabolism in vitro --- p.93 / Chapter 3.2.4 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.94 / Chapter 3.2.5 --- Calibration curves --- p.95 / Chapter 3.2.6 --- Data analysis --- p.95 / Chapter 3.3 --- Results --- p.96 / Chapter 3.3.1 --- Effects of danshen extract and its components on warfarin metabolism by using human pooled liver microsomes --- p.96 / Chapter 3.3.2 --- Effects of danshen extract and its components on S-warfarin metabolism by using human lymphoblast CYP2C9 isoform --- p.103 / Chapter 3.4 --- Discussion --- p.111 / Chapter Chapter 4 --- Effects of acute and subchonic pretreatment of danshen extract on the pharmacokinetics of warfarin in the rats in vivo --- p.115 / Chapter 4.1 --- Introduction --- p.115 / Chapter 4.2 --- Materials and methods --- p.118 / Chapter 4.2.1 --- Chemicals and reagents --- p.118 / Chapter 4.2.2 --- Animals Table of Contents --- p.118 / Chapter 4.2.3 --- Effects of acute danshen extract pretreatment on the pharmacokinetics of warfarin --- p.119 / Chapter 4.2.4 --- Effects of subchronic danshen extract pretreatment on the pharmacokinetics of warfarin --- p.119 / Chapter 4.2.5 --- Steady state warfarin study --- p.120 / Chapter 4.2.6 --- Sample extraction --- p.120 / Chapter 4.2.7 --- High Pressure Liquid Chromatography (HPLC) analysis --- p.121 / Chapter 4.2.8 --- Calibration curve --- p.121 / Chapter 4.4 --- Results --- p.123 / Chapter 4.3.1 --- Effects of acute danshen extract pretreatment on the pharmacokinetics of warfarin --- p.123 / Chapter 4.3.2 --- Effects of subchronic danshen extract pretreatment on the pharmacokinetics of warfarin --- p.128 / Chapter 4.3.3 --- Steady state warfarin study --- p.136 / Chapter 4.5 --- Discussion --- p.138 / Chapter Chapter 5 --- Effects of danshen extract on the absorption of warfarin by using Caco-2 cells model --- p.142 / Chapter 5.1 --- Introduction --- p.142 / Chapter 5.2 --- Materials and methods --- p.144 / Chapter 5.2.1 --- Materials for Caco-2 cells culture experiment --- p.144 / Chapter 5.2.2 --- Preparation of Caco-2 monolayer --- p.144 / Chapter 5.2.3 --- High Pressure Liquid Chromatography (HPLC) analysis for warfarin --- p.145 / Chapter 5.2.4 --- Calibration curve --- p.145 / Chapter 5.2.5 --- Stability test for warfarin and danshen extract --- p.145 / Chapter 5.2.6 --- Toxicity test of danshen extract on Caco-2 cells --- p.146 / Chapter 5.2.7 --- Transport study --- p.146 / Chapter 5.2.8 --- Data Analysis --- p.147 / Chapter 5.3 --- Results --- p.149 / Chapter 5.3.1 --- Stability of warfarin and danshen extract --- p.149 / Chapter 5.3.2 --- Toxicity test of danshen extract on Caco-2 cells --- p.149 / Chapter 5.3.3 --- Integrity of Caco-2 cells monolayer --- p.152 / Chapter 5.3.4 --- Transport study --- p.152 / Chapter 5.4 --- Discussion --- p.154 / Chapter Chapter 6 --- General discussion --- p.156 / References --- p.163

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_324897
Date January 2004
ContributorsWu, Wai Ping., Chinese University of Hong Kong Graduate School. Division of Pharmacology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, 177 leaves : ill. ; 30 cm.
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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