Grapefruits & Drug Metabolism

By: Rose Al Abosy

Every time I am prescribed a medication, I read through the information packet. The last medication I picked up at Walgreens had one line that stuck out: “Avoid eating grapefruit or drinking grapefruit juice...these can affect the amount of [the drug] in the blood.” I was immediately reminded of brunch I had one Saturday morning last year with a close friend. I wanted a glass of fresh squeezed juice, either orange or grapefruit, and my friend told me a quick little anecdote about grapefruit juice. They never had it in the house because everyone in his family had high blood pressure and “you can’t drink grapefruit juice on blood pressure meds.”

I just took his word for it at the time, but reading it in the information packet for my own meds made me investigate. Turns out, it comes down to drug metabolism. Cells that line the lumen of the gut have to absorb drugs and pass them to the liver so they can enter the blood and be circulated systemically. This process can rely on specific transporters at each stage, from absorption to re-circulation. The cells that absorb materials from the gut have enzymes that begin the metabolism of the drug. As a result, the amount of the drug that circulates is less than what you originally took orally. Doctors take this reduction in drugs into account when prescribing the amount of medication a patient should take. Calculating drug dosage is always based on how much active drug eventually ends up in the blood and takes into consideration how strong the degradation response against the drug is.

One important family of enzymes that are involved in this process are the cytochrome P450 enzymes (CYPs), one of which is CYP3A4. This enzyme is found in the liver and the epithelial cells of the small intestine where it metabolizes a lot of commonly prescribed drugs, like statins (which are for high cholesterol, but can also be used to treat high blood pressure).

So what does this have to do with grapefruit? CYP3A4 is inhibited by molecules called furanocoumarins, like bergamottin and dihydroxybergamottin, and with CYP3A4, the drug undergoes less processing in the gut and liver. It can take up to 72 hours to regain full enzyme activity after inhibition, so consuming furanocoumarins can inhibit drug processing for well over a day. Of course, these furanocoumarins just happen to be found in grapefruits. That means drinking grapefruit juice along with taking a drug that is metabolized by CYP3A4 can lead to a higher dose of the drug in your blood than intended by your doctor, which in some cases can be fatal. And remember those transporters that aid in moving the drug into the cells of your body? Those transports are also affected by grapefruit juice, either blocking their activity or downregulating their expression, which can lead to a lower dose of the drug in your blood. Thus, medications can greatly affect the final concentration of our medications in our blood—either by increasing it by blocking natural decomposition of it in our guts, leading to an increase in the final drug concentration, or by blocking transporters of the drug, leading to a decrease in the final drug concentration.

Even abundant and naturally found chemicals like the furanocoumarins in grapefruit can modulate drug metabolism, causing a higher or lower concentration of the drug than expected. For your own health, verify whether your medications are affected by grapefruit consumption, and always talk to your doctor if you have any concerns.

The reason our bodies have these systems in place is to make sure nothing dangerous enters our bodies. As medical drugs we take are foreign to our systems, our bodies automatically begin the process of degrading them. Of course, these degrading processes take time and have a certain threshold of how many molecules they can process, meaning that we can override these systems to ensure drug delivery. Additionally, drug development can also take advantage of these pathways, designing drugs that are usually inactive, until they go through lumen cells that cleave the drug into its active form.