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Application Of Early Drug Metabolism In Scientific Evaluation Of Traditional Chinese Medicine

Posted on:2007-01-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:1104360185461391Subject:Biochemical Engineering
Abstract/Summary:PDF Full Text Request
Increasing attention is being paid to how we can make the scientific evaluation for safety of Traditional Chinese Medicine (TCM). Following the integration of early absorption, distribution, metabolism, excretion and toxicity (eADME/T), in particular the study of early metabolic and toxic properties into the scientific evaluation of TCM, the successful experiences in western and modern drug discovery and development will enormously accelerate the process.In the scientific evaluation of TCM, there is an important issue, namely the risk assessment for potential TCM-prescription drug interactions. In the present study, the potential for TCM-prescription drug interactions was predicted by the early evaluation of drug metabolic properties. In term of the characteristics of TCM, we firstly proposed that the biotransformation of TCM in human gastrointestinal tract should be integrated into the early evaluation of drug metabolic properties. We also validated this issue using the in vitro experiments, where a set of ginsenosides was selected as model chemicals. In most cases, ginseng products are orally administered. However, the absorption of naturally occurring ginsenosides (NOGs) from the intestines is very poor. The majority of naturally occurring ginsenosides is not able of reaching liver, exerting an influence on metabolic enzymes. There is still no consensus about the in vivo influence of ginseng on cytochrome P450 (CYPs).Utilizing a set of ginsenosides, we found that in the in vitro experiments, the NOGs exhibited no inhibition or weak inhibition against human CYPs activities; however, the degradative products in human gastrointestinal tract, Rh1 and F1, and the intestinal bacteria metabolites, Compound K (C-K), protopanaxadiol (Ppd), and protopanaxatriol (Ppt), from NOGs, which may reach the systemic circulation going through liver after oral administration of ginseng extract, demonstrate a...
Keywords/Search Tags:eADME/T, cytochrome P450, biotransformation in human gastrointestinal tract, ginsenosides, indirect drug-drug interactions
PDF Full Text Request
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