Enzyme Inhibitor
Agent which competes with another drug for binding at enzymatic site
Rate of substrate metabolism is decreased, resulting in increased drug concentrations
Inhibitors vary in selectivity and potency
Protease inhibitors are CYP3A inhibitors
Notes:
- A P450 enzyme inhibitor is any drug that inhibits the metabolism of a P450 substrate
- This inhibition process is generally competitive in nature (I.e., the inhibitor competes with a substrate for binding at the enzyme’s binding site), and is reversible.
- This competitive mechanism results in accumulation of the target drug (substrate). However, once the inhibitor is gone, metabolism is back to normal.
- NB: a drug does not necessarily need to be a P450 substrate to be an enzyme inhibitor (e.g., fluconazole is primarily renally excreted, but is a moderate to weak P450 inhibitor)
- Enzyme inhibitors vary in both selectivity and potency, in terms of their effects on CYP enzymes.