Related Experiment Video
Updated: Jun 22, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Application of mechanism-based CYP inhibition for predicting drug-drug interactions
1RMIT University, Discipline of Chinese Medicine, School of Health Sciences, Bundoora, Victoria, Australia.
Background:
A mechanism-based inhibition of CYPs is characterized by NADPH-, time- and concentration-dependent enzyme inactivation and substrate protection. A significant inactivation of CYPs and particularly the main human hepatic and intestinal CYPs could result in clinical drug-drug interactions (DDIs) and adverse drug reactions.
Objective:
To address whether DDIs owing to mechanism-based CYP inhibition is predictable based on in vitro inhibitory data.
Method:
Medline (by means of PubMed up to 26 March 2009) has been searched using proper relevant terms.
Result/Conclusion:
It is possible to predict DDIs caused by mechanism-based CYP inhibition, although the in vitro data do not necessarily translate directly into relative extents of inhibition in vivo because in vivo clinical consequences depend on additional factors that are not easily accounted for in vitro and for reversible inhibition. Incorporation of other important parameters such as CYP degradation rate (k(deg)), relative contribution of the CYP inactivated to the victim drug elimination (f(m(CYP))) and inhibition of intestinal CYP-mediated first-pass metabolism of the object drug (F'(gut)/F(gut) ratio) into the prediction models significantly improves the prediction. Uncertainty of the prediction is mainly from the variability in the estimates of these critical parameters.
Related Concept Videos
Pharmacokinetics: Drug–Drug Interactions
Drug toxicity: Drug–Drug Interaction
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacokinetics: Drug–Food and Drug–Viral Interactions
Protein-Drug Binding: Mechanism and Kinetics
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
Pharmacogenetics of Drug Metabolism: Overview

