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dc.titlePredicting pharmacokinetic herb-drug interactions
dc.contributor.authorZhou, S.
dc.contributor.authorChan, E.
dc.contributor.authorLi, S.C.
dc.contributor.authorHuang, M.
dc.contributor.authorChen, X.
dc.contributor.authorLi, X.
dc.contributor.authorZhang, Q.
dc.contributor.authorPaxton, J.W.
dc.identifier.citationZhou, S.,Chan, E.,Li, S.C.,Huang, M.,Chen, X.,Li, X.,Zhang, Q.,Paxton, J.W. (2004). Predicting pharmacokinetic herb-drug interactions. Drug Metabolism and Drug Interactions 20 (3) : 143-158. ScholarBank@NUS Repository.
dc.description.abstractIn vitro and in vivo studies have indicated that the induction or inhibition of cytochrome P450 (CYP) is one of the major mechanisms for some clinically important pharmacokinetic herb-drug interactions. Thus, an attempt was made to predict pharmacokinetic herb-drug interactions using the pharmacokinetic principles that are used for predicting drug-drug interactions. The expected AUC ratio was mainly dependent on unbound herbal inhibitor concentration ([I]) and inhibition constant (Ki), hepatic fraction (fh), number of inhibitory herbal constituents (n) and metabolic pathway fraction in hepatic metabolism (fm). Herb-drug interactions would be with low risk if ∑ i=1 n [[I i]/Ki(i)] is less than 0.1, medium risk if it is between 0.1 and 1.0, and high risk if it is greater than 1. For high clearance drugs, the change of fh × fm had minor influence on AUC ratio when ∑i=1 n [[Ii]/Ki(i)] values were fixed. Similarly, fm did not affect the AUC ratio for low clearance drugs. It appeared likely to predict a herb-drug metabolic interaction when [I], Ki, fh, fm and n could be determined. However, many herb- and drug-related factors may cause difficulties with the prediction, and well-designed human studies are always necessary.
dc.subjectCytochrome P450
dc.subjectDrug interactions
dc.subjectMetabolic inhibition
dc.description.sourcetitleDrug Metabolism and Drug Interactions
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