P-Glycoprotein inhibitors can and do affect the concentrations of other drugs. I will be honest in that when I think about drug interactions, it isn’t the first thing that comes to mind. This gut transporter can impact clinical care and influence drug decisions.

What is P-Glycoprotein?

P-Glycoprotein is an efflux transporter that is found in the gut. Depending upon the molecule, this transporter can act by pumping it back into the gut. This essentially blocks absorption into systemic circulation and causes lower blood levels.

How does It Impact Drugs?

By essentially pumping drugs back into the gut, it can substantially reduce the systemic concentration of numerous drugs. A lower concentration of a drug in the systemic circulation means that there is a greater risk of treatment failure. Many drugs are dosed to factor in this lower concentration by the activity of the transporter. Where it gets tricky is when we add another drug that may inhibit or induce it.

How do Drugs Affect P-Glycoprotein?

There is a significant list of drugs that can affect this transporter (see list at end of the post). Drugs can act one of two ways. By inhibiting P-glycoprotein, this can lead to higher concentrations of drugs that are effluxed into the gut by the transporter. By inducing it, we essentially increase the activity of the transporter and pump more of the affected drug into the gut and prevent it from getting into circulation. The end result: An inhibitor can cause higher concentrations and an inducer can cause lower blood concentrations.

Interestingly, many drugs that affect P-glycoprotein also impact CYP3A4.

Common P-Glycoprotein Inhibitors (not all-inclusive)

• Amiodarone (listen to podcast)
• Carvedilol
• Macrolides
• Some of the Azole antifungals
• Verapamil

Common Inducers (not all-inclusive)

• Phenytoin
• Rifampin
• Carbamazepine
• St. John’s Wort (example enzyme induction drug interaction)

Drugs Affected By P-Glycoprotein Inhibitors and Inducer

The primary reason I wanted to provide this information was that some of the newer anticoagulants are significantly affected by these agents. We tend to think that since there are less drug interactions with the newer agents compared to warfarin, that they don’t have any. Apixaban requires dose adjustments (reduction) for patients who are taking a drug like ketoconazole. For those taking inducers, it is not recommended to take apixaban. Two other DOACs like rivaroxaban and dabigatran also have adjustments and contraindications with p-glycoprotein inhibitors/inducers. Be sure to review that medication list in patients who are placed on these agents for clot prophylaxis, DVT, and atrial fibrillation.

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