Grapefruit food-drug interaction (inhibition) ∞
The mechanism of herb-drug interaction with St. John's Wort has been elucidated, and the greatest concern is focused on medications that are substrates on CYP3A4; this enzyme degrades many drugs. St. John's Wort induces production of the enzyme, hence the drugs are degraded faster. This is the same enzyme that is inhibited by grapefruit juice, which has the opposite effect of increasing drug levels in the blood. Both St. John's Wort and grapefruit juice are among the strongest of the known natural substances that affect drug levels when consumed at ordinary doses. In addition to CYP3A4, St. John's Wort affects phosphorylated glycoprotein (P-glycoprotein or Pgp), which also metabolizes drugs. Aside from indinavir, the metabolism of other protease inhibitor anti-HIV drugs are also affected by St. John's Wort.
One of the best studied examples of food-drug interactions is the inhibition and inactivation of the CYP3A4 and CYP1A2 enzymes by grapefruit juice. The effects of grapefruit juice on many commonly used drugs, such as cyclosporin and felodipine, have the potential to require dosage adjustment to maintain drug concentrations within their therapeutic windows.