CYP P450 inhibition


Some drugs are able to block the activity of the microsomal enzymes and thus decrease the clearing ability of the liver. These are called inhibitors. As shown in the graphic, when an inhibiting drug is added to steady-state concentrations of a drug which is a substrate, this leads to a reversible decrease in enzyme activity resulting in an increase in the substrates serum concentrations.

Unlike enzyme induction, inhibition usually begins with the first dose of the inhibitor. Inhibition is maximal when the inhibitor reaches steady state.L ook at the clinical example shown in the table where a patient is taking a daily dose of a coumarin in order to lower the risk of a DVT.

This patient then gets prescribed metronidazole (a known enzyme inhibitor). It is possible that the serum concentration of the coumarin will be now be increased to the point where the patient is receiving too much anticoagulation and is at risk of a significant bleed.

See how an inhibitor effects the concentration of another drug by clicking here and selecting "add inhibitor".


A patient with an acute urinary tract infection develops a reduced renal function (GFR 50%). She is treated for epilepsy with levetiracetam. Levetiracetam is cleared via the kidneys, so the dose is halved. When the patient is recovering from the infection and the kidney function is restored, how will this change the pharmacokinetic parameters of levetiracetam?