Did you know that over 50% of the prescription drugs on the market have the potential to interact with grapefruit and grapefruit juice? It's a surprising statistic, but it is true.
The reason is that many drugs are metabolized and broken down by an enzyme system called the "cytochrome P450" system. There are many different sub-enzymes, but the most prominent in the group is the cytochrome P450 3A4 enzyme - CYP3A4 for short. Over 50% of the drugs on the market are impacted by this enzyme.
Grapefruit contains chemicals called furanocoumarins which are able to bind to the CYP3A4 enzyme and inactivate it. This enzyme inactivation primarily occurs in the gut rather than in the liver. This inactivation means that drugs that are normally broken down and metabolize by CYP3A4 are no longer broken down to the same extent. Ultimately, it means that levels of drugs in the body can be increased, resulting in drug toxicity and adverse effects. Since the enzyme inactivation occurs in the gut, it means more drug gets absorbed into the body, resulting in higher peak concentrations (Bailey, CMAJ 2013).
In addition to affecting the CYP3A4 enzymes, grapefruit can also interact with drugs in other ways. Grapefruit also has effects on so-called "drug transport proteins," specifically P-glycoprotein and organic anion transporting polypeptides (OATP) (DI Marco, Life Sci 2002, Greenblatt, J Clin Pharmacol 2009). P-glycoprotein is involved in pumping drugs out of cells whereas OATP is involved in carrying drugs into cells.
Here are some key points to remember regarding these interactions: