Quotient Bioresearch Blog

Drug-drug Interactions; using In Vitro techniques

  

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Drug-drug interactions (DDI) are a common issue during drug treatment and give rise to a large number of hospital admissions within the EU. During the past 20 years, scientific progress has made it possible to predict clinically relevant pharmacokinetic drug interactions based on a limited number of in vitro and in vivo studies.

    EMA and FDA Guidance on DDI Assessment

The European Medicines Agency (EMA) has recently released a draft guideline regarding the investigation of drug interactions (CPMP/EWP/560/95/Rev. 1, April 2010). Previously, the FDA had issued draft guidance regarding the drug-drug interaction assessment of new drugs (September 2006) and how in vitro methods in particular may be used to assess the interaction potential of new drugs.

UPDATE added February 2012 - Please note that on Friday 17 February 2012 the FDA released revised draft guidance to their 2006 draft guidance Drug Interaction Studies - Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations.

Quotient will revise the current publication associated with this blog article shortly to reflect this new draft guidance.

Predicting DDIs using In Vitro Techniques

The advances in in vitro science over the last decade, coupled with increasingly sophisticated models and instrumentation mean that scientists can make accurate predictions about certain kinds of DDI in vivo. This means that the interactions which caused high profile drug withdrawals during the late 1990s can now be largely predicted and therefore prevented.

"The Role of In Vitro Studies in Assessing Drug-drug Interactions"

Guy Webber, Head of In Vitro Sciences at Quotient Bioresearch has authored a highly informative article (International Pharmaceutical Industry; Autumn 2010) comparing the main aspects of these guidance documents with particular emphasis on the increasing importance of using in vitro methods to assess and predict drug-drug interactions in vivo.    

CYP450 Inhibition

Inhibition of CYP450 is the major cause of DDIs. Both the FDA and EMA recommend that the inhibition of CYP450 enzymes be assessed using in vitro methods, and the agencies suggest a similar study design. In this article, the recommendations and differences in experimental design are explained. The article also reviews guidance for;

• Time-dependent CYP inhibition
• CYP450 induction
• Use of human hepatocytes to characterise enzymology of new drugs
• Drug transporter interactions

Learn how the advances in in vitro technology can predict drug-drug interactions and prevent expensive late discoveries, or even drug withdrawal.

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