Drug Interactions Newsletter

Volume 2, Issue 22, 06/01/2010

Question

What does it mean for a drug to be a mechanism-based inhibitor of cytochrome P-450 (CYP) 3A4?

Answer

Periodically, the editorial board will release an issue related to explaining principles or terms that all clinicians should be familiar with as many times these will come up in clinical practice.  They are also concepts built upon in many of the newsletters. 

It is well known that the cytochrome P-450 (CYP) enzyme system is involved in the drug metabolism of many medications used in clinical practice and have been implicated in causing clinically relevant drug-drug interactions.(1,2)  There are a number of CYP450 enzymes involved in mediating drug interactions and commonly include CYP1A2, 2C9, 2C19, 2D6, and 3A4.(1)  Of these CYP enzymes, CYP3A4 is not only the most prevalent CYP enzyme in the liver, but is used by more than 50% of medications on the market for their metabolism and elimination from the body.(1)  The problem occurs when in the metabolism of these substrates of CYP3A4 also result in the inhibition of CYP3A4.  A number of medications are known to be inhibitors of CYP3A4, but they differ in the degree of inhibition they have on the enzyme and the type of inhibition they confer.(1)  One type of inhibition of CYP3A4 is mechanism-based inhibition.(3).... 

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