The interaction between grapefruit juice and certain antihistamines leading to cardiotoxicity is explained by inhibition of which enzyme?

• A. Displacement from protein binding
• B. Decreased urinary excretion
• C. Inhibition of the CYP3A4 enzyme
• D. Increased absorption

Answer: (C)

Grapefruit juice inhibits the intestinal enzyme CYP3A4, which is responsible for metabolizing many antihistamines. When this enzyme is blocked, the drug isn’t broken down as efficiently, so its levels in the blood rise. Those higher levels can cause cardiotoxic effects such as QT prolongation and serious arrhythmias. This metabolic inhibition, not changes in protein binding, excretion, or absorption, explains why grapefruit juice can lead to dangerous interactions with certain antihistamines.