title: Predicting pharmacokinetic herb-drug interactions.
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.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore. phazsf@nus.edu.sg
authors.forename: Shufeng
authors.initials: S
authors.lastname: Zhou
authors.forename: Eli
authors.initials: E
authors.lastname: Chan
authors.forename: Shu Chuen
authors.initials: SC
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: James W
authors.initials: JW
authors.lastname: Paxton
mesh_terms: D019540:Area Under Curve; D003577:Cytochrome P-450 Enzyme System / Q000493:pharmacokinetics*; D020441:Ginkgo biloba / Q000378:metabolism*; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D020944:Silybum marianum / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D003577:Cytochrome P-450 Enzyme System