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Title: Predicting pharmacokinetic herb-drug interactions
Authors: Zhou, S. 
Chan, E. 
Li, S.C. 
Huang, M.
Chen, X.
Li, X.
Zhang, Q.
Paxton, J.W.
Keywords: Cytochrome P450
Drug interactions
Metabolic inhibition
Issue Date: 2004
Citation: Zhou, 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.
Abstract: In 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.
Source Title: Drug Metabolism and Drug Interactions
ISSN: 07925077
Appears in Collections:Staff Publications

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