The grapefruit juice interaction with Pimozide is due to inhibition of which enzyme?

• A. CYP2D6
• B. CYP2C9
• C. CYP1A2
• D. CYP3A4

Answer: (D)

Grapefruit juice can dramatically raise pimozide levels because it inhibits an intestinal enzyme used to metabolize many oral drugs. The compounds in grapefruit juice (furanocoumarins) cause mechanism-based inactivation of CYP3A4 in the gut, so less pimozide is broken down during first-pass metabolism. With reduced intestinal metabolism, more of the drug enters the bloodstream, increasing exposure and the risk of serious effects like QT prolongation and torsades de pointes. The other enzymes listed aren’t the ones grapefruit juice targets to produce this interaction, so their inhibition wouldn’t explain the rise in pimozide levels. This effect is particularly relevant for oral dosing and can persist for days because new CYP3A4 has to be synthesized to restore metabolism.