In contrast to CYP 450 enzyme interference, these mechanisms of interaction are competitive and relatively short-lived. Of additional interest is the interference with P-glycoprotein and organic anion transporting peptides by grapefruit bioactive compounds. 3 With many oral therapeutic agents undergoing first-pass metabolism by CYP 450 3A4, the effects of enzyme inhibition can be significant. This inhibition of intestinal clearance by CYP3A4 requires de novo restoration of the isoenzyme prior to returning to normal metabolic function. 2 Mechanism-based inhibition of CYP 450 3A4 enzymes in the intestine by furanocoumarins results in a complete inactivation of the enzyme. Furanocoumarin derivatives include bermagottin, bergapten, bergaptol, and 6’,7’-dihydroxybermagottin. Active chemical compounds in grapefruit, known as the furanocoumarins, are primarily responsible for the CYP 450 3A4 interaction. Cytochromes are the major enzymes through which drug metabolism and bioactivation processes occur, accounting for nearly 75% of these metabolic reactions. The CYP 450 system is a diverse family of over 60 enzymes that function to catalyze the oxidation of organic substances. 1 The CYP 450 3A4 enzyme is an isoform of the CYP 450 system. The interference of intestinal cytochrome P-450 (CYP 450) enzymes by grapefruit furanocoumarin derivatives is currently accepted as the primary mechanism of interaction. The well-documented interaction between grapefruit and grapefruit-containing products and certain medications has been attributed to several different potential mechanisms of interaction. Yet, grapefruit has been linked to many significant drug interactions.
Grapefruit is an excellent source of vitamins and phytochemicals.
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