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Predicting drug-drug interactions: an FDA perspective.
Lei Zhang1, Yuanchao Derek Zhang, Ping Zhao
1Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Rm 3188, Bldg 51, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA.
The AAPS Journal
|May 7, 2009
Summary
Evaluating drug-drug interaction potential is crucial for new drugs. In vitro studies are vital screening tools to predict interactions and guide further drug development and labeling.
Area of Science:
- Pharmacology
- Drug Development
- Toxicology
Background:
- Pharmacokinetic drug interactions can cause serious adverse events.
- Assessing drug-drug interaction (DDI) potential is essential for new molecular entities (NMEs) during development and regulatory review.
- Altered drug exposure due to concomitant medications can impact NME safety and efficacy.
Purpose of the Study:
- To summarize critical elements in the in vitro evaluation of drug interaction potential during drug development.
- To highlight the impact of in vitro data on drug labeling through a case study.
- To discuss the role of in vitro and in silico methods in predicting drug interactions.
Main Methods:
- Review of in vitro methodologies for predicting in vivo drug interactions.
- Discussion of in silico modeling and simulation for drug interaction assessment.
- Analysis of FDA draft guidance on drug interaction studies and labeling.
Main Results:
- In vitro studies are a critical first step in assessing drug interactions.
- Well-designed in vitro studies can screen for the need for in vivo assessment and inform study design.
- In silico methods can complement in vitro experiments for interaction prediction.
Conclusions:
- In vitro drug interaction evaluation is integral to drug development.
- In vitro data significantly influences drug labeling and regulatory decisions.
- A comprehensive approach using in vitro and in silico tools aids in predicting and managing drug interactions.
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