Prediction of Herb–Drug Metabolic Interactions: a Simulation Study

Authors

Shufeng Zhou, National University of SingaporeFollow
Min Huang, National University of Singapore
Anlong Xu, National University of Singapore
Hongyuan Yang, National University of Singapore
Wei Duan, National University of Singapore
James W. Paxton, National University of Singapore

Document Type

Article

Publication Date

6-2005

Keywords

herb, metabolic inhibition, cytochrome P450, drug interactions

Digital Object Identifier (DOI)

https://doi.org/10.1002/ptr.1559

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. An attempt was made to simulate the effects of herbal preparation with single or multiple CYP-inhibiting constituents on the area of the plasma concentration-time curve (AUC) of coadministered drug that was either a low clearance drug by intravenous (i.v.) injection or a high clearance drug by oral route. Our simulation studies indicated that the expected increase (R_c) in the AUC of the coadministered drug by inhibiting herbal constituent(s) was dependent on the route of administration. For low clearance drug by i.v. injection, R_c was generally determined by inhibition constant (K_i), unbound inhibitor concentration ([I]), hepatic fraction (f_h), number of inhibitory herbal constituents (n) and metabolic pathway fraction in hepatic metabolism (f_m), while R_c for a high clearance drug by oral route, R_c was determined by K_i, [I], n and f_m. By varying these parameters, R_c changed accordingly. It appeared likely to predict a herb–drug metabolic interaction, if the inhibiting herbal constituents could be quantitatively determined. However, many herb- and drug-related factors may cause difficulties with the prediction, and thus in vivo animal and human studies are always necessary.

Was this content written or created while at USF?

No

Citation / Publisher Attribution

Phytotherapy Research, v. 19, issue 6, p. 464-471

Scholar Commons Citation

Zhou, Shufeng; Huang, Min; Xu, Anlong; Yang, Hongyuan; Duan, Wei; and Paxton, James W., "Prediction of Herb–Drug Metabolic Interactions: a Simulation Study" (2005). Pharmacy Faculty Publications. 26.
https://digitalcommons.usf.edu/pharm_facpub/26