What are P450 Inhibitors?

Carey Reeve

P450 refers to a family of metabolic proteins called the cytochrome P450 enzymes; they are responsible for breaking down drugs inside the body. P450 inhibitors slow or stop the chemical action of a cytochrome P450 enzyme usually by binding with the enzyme before it can do its job. Certain drugs are known to be P450 inhibitors, but some foods can inhibit these enzymes too. It’s useful in some cases to purposefully inhibit the P450 enzymes because they break some medications down before the medication can work. In other cases, medications and foods that inhibit the enzymes’ function must be avoided so that a medication breaks down quickly enough and doesn’t build up in the body.

Using tobacco products can inhibit P450 enzymes.
Using tobacco products can inhibit P450 enzymes.

Large concentrations of cytochrome P450 enzymes are found in the liver, but they can be found in many other organs as well like the kidneys and digestive tract. These enzymes begin the process of breaking down many different substances that could become toxic if not excreted in the urine or bile. The substances include medications, illegal drugs, steroid hormones, and other organic molecules.

Consuming grapefruit can inhibit P450 enzymes.
Consuming grapefruit can inhibit P450 enzymes.

A wide range of medications act as P450 inhibitors. This inhibition — along with the opposite effect, induction — is what is responsible for most drug interaction problems and can cause some medications to build up to toxic levels in the body. Many antidepressants like Prozac, Zoloft, and Luvox are inhibitors of certain P450 enzymes along with Tagemet, Cipro, Benadryl and a long list of other medications. Consuming grapefruit, grapefruit juice, starfruit, watercress, and even using tobacco products also inhibit these enzymes.

Some medications are no longer used in the United States because of life-threatening side effects caused by interactions with other drugs that are P450 inhibitors. Examples include Seldane, Hismanal, Propulsid. Another medication, Posicor, has been discontinued because it is itself is a strong P450 inhibitor that reacted dangerously with some heart medications.

One important point is that some drugs are less effective by becoming metabolized more quickly while other drugs are actually more effective. Drugs already in the chemical form that are biologically active do not relieve symptoms as well if there is high cytochrome P450 activity. They may work better if taken with P450 inhibitors. Other drugs are taken in an inactive form and are activated by the first stages of breaking down. These drugs may not perform their function well if the patient also takes a cytochrome P450 inhibitor.

Starfruit may break down some medications before they can work.
Starfruit may break down some medications before they can work.

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