Evaluation of models for predicting drug–drug interactions due to induction
- 26 August 2010
- journal article
- research article
- Published by Taylor & Francis Ltd in Expert Opinion on Drug Metabolism & Toxicology
- Vol. 6 (11), 1399-1416
- https://doi.org/10.1517/17425255.2010.516251
Abstract
Importance of the field: Drug–drug interactions caused by induction of metabolizing enzymes, particularly CYP3A, can impact the efficacy and safety of co-administered drugs. It is, therefore, important to understand a new compound's potential for enzyme induction and to understand how to use the induction data generated in vitro to predict potential for drug–drug interactions in vivo. Areas covered in this review: Recent advances in methods for using in vitro data to predict potential for CYP3A induction in vivo are reviewed. What the reader will gain: The reader will gain a comprehensive understanding of the advantages and disadvantages of various prediction methods for induction and be able to directly compare different methods using a common in vitro data set. Take home message: The various methods for predicting clinical CYP3A induction from in vitro induction data all have demonstrated utility; it is the authors' opinion that the correlation-based approaches offer as good or better predictivity and have simpler input requirements than more complex approaches. Of the different correlation approaches, the relatively simple unbound Cmax/EC50 or AUC/EC50 approaches are the simplest and yet show the best correlation to the observed clinical data. While the approaches discussed herein represent an improvement in our understanding of the predictive value of in vitro induction data, it is important to recognize that there is still room for improvement in quantitative prediction of magnitude of drug interactions due to induction.Keywords
This publication has 46 references indexed in Scilit:
- Cytochrome P450 3A4 mRNA Is a More Reliable Marker than CYP3A4 Activity for Detecting Pregnane X Receptor-Activated Induction of Drug-Metabolizing EnzymesDrug Metabolism and Disposition, 2010
- Comparison of different approaches to predict metabolic drug-drug interactionsXenobiotica, 2007
- Use of Immortalized Human Hepatocytes to Predict the Magnitude of Clinical Drug-Drug Interactions Caused by CYP3A4 InductionDrug Metabolism and Disposition, 2006
- DURATION OF PLECONARIL EFFECT ON CYTOCHROME P450 3A ACTIVITY IN HEALTHY ADULTS USING THE ORAL BIOMARKER MIDAZOLAMDrug Metabolism and Disposition, 2006
- Induction of Drug Metabolism Enzymes and MDR1 Using a Novel Human Hepatocyte Cell LineThe Journal of pharmacology and experimental therapeutics, 2004
- Clinical Pharmacology of Bosentan, a Dual Endothelin Receptor AntagonistClinical Pharmacokinetics, 2004
- Pharmacokinetic Interactions with RifampicinClinical Pharmacokinetics, 2003
- Steady‐State Pharmacokinetics and Tolerability of Modafinil Administered Alone or in Combination with Dextroamphetamine in Healthy VolunteersThe Journal of Clinical Pharmacology, 2002
- RitonavirClinical Pharmacokinetics, 1998
- Concentrations and Effects of Oral Midazolam are Greatly Reduced in Patients Treated with Carbamazepine or PhenytoinEpilepsia, 1996