Predicting pharmacokinetic herb-drug interactions.

Zhou, S, Chan, E, Li, S, Huang, M, Li, X, Zhang, Q and Paxton, J 2004, 'Predicting pharmacokinetic herb-drug interactions.', Drug Metabolism and Drug Interactions, vol. 20, no. 3, pp. 145-158.


Document type: Journal Article
Collection: Journal Articles

Title Predicting pharmacokinetic herb-drug interactions.
Author(s) Zhou, S
Chan, E
Li, S
Huang, M
Li, X
Zhang, Q
Paxton, J
Year 2004
Journal name Drug Metabolism and Drug Interactions
Volume number 20
Issue number 3
Start page 145
End page 158
Total pages 14
Publisher Freund Publishing House, Ltd.
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 sigma(i=1)n [[Ii]/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 x fm had minor influence on AUC ratio when sigma(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.
Subject Traditional Chinese Medicine and Treatments
Keyword(s) cytochrome P450
drug interactions
herb
metabolic inhibition
ISSN 0792-5077
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