Oral administration of grapefruit juice increases the bioavailability of a variety of drugs, including felodipine, midazolam, saquinavir, and verapamil. After oral administration of any one of these drugs, which of the following is most likely to be increased in the presence of grapefruit juice?
A.Hepatic CYP3A4 activity
B.Intestinal drug metabolism
C.Peak serum concentration
D.Total body clearance
E.Volume of distribution
Explanation
Recent studies have demonstrated that grapefruit juice contains chemicals called furanocoumarins which have been shown to inhibit drug metabolism by interfering with the hepatic cytochrome P450 system, especially CYP3A4. Inhibiting a drug’s hepatic metabolism can lead to higher peak serum concentrations (choice C) of that drug.
Hepatic CYP3A4 activity (choice A) would be decreased by the furanocoumarins in grapefruit juice.
Intestinal drug metabolism (choice B) should not be affected because grapefruit juice inhibits hepatic drug metabolism.
Total body clearance (choice D) and volume of distribution (choice E) of the aforementioned drugs should both decrease. Volume of distribution is the ratio of the amount of drug in the body versus the plasma drug concentration. If the plasma drug concentration increases because drug metabolism is decreased, then volume of distribution will decrease. Clearance is the ratio of the rate of elimination of a drug to the plasma drug concentration. If the plasma drug concentration increases, then clearance will decrease.