As you know, our bodies have systems that break down foreign substances before they can be absorbed. Consider that while medications are given for a reason, from the body’s perspective, they are foreign substances that need to be eliminated. One of the stars of the “disposal” system is the enzyme system known as cytochrome P-450 (CYP3A4), which is present in the liver — the organ that does the majority of the breakdown. It is also found in the walls of our digestive tract, serving as a gatekeeper to limit absorption.
The bottom line is that only a portion of any medication taken orally ends up in our general circulation; this is factored into the determination of therapeutic doses. (Meds that tend to be completely destroyed must be given via other means, such as an injection, which avoids what’s referred to as “first pass metabolism.”)
The connection with grapefruit is that the furanocoumarins prevent CYP3A4 from doing its job. This can result in higher-than-desired levels of medications in the body. The levels are not only elevated, but also they remain so for extended periods.
The effect was discovered by accident when grapefruit juice was used to disguise the taste of treatments used in a research study. The results did not match expectations, and it was found that the juice itself affected how the treatments were absorbed and broken down. More studies followed, leading to an understanding of how the processing of medications “handled” by CYP3A4 was changed when furanocoumarins were around. In one study, the effect was still noted 24 hours after grapefruit juice was consumed.