from "Grapefruit Juice and Drug Interactions"
Jessica R. Oesterheld, M.D.
...Gfj is a competitive and mechanism-based inhibitor, (similar in potency to TAO) of intestinal CYP 3A4 and CYP 3A5 but not of liver CYPs (Schmeidlin-Ren 1997). Inhibition occurs almost immediately if the gfj dose is high enough (e.g., a single glass of reconstituted frozen concentrate inhibits CYP3A4 within the first 4 hours. Schmiedlin-Ren 1997). Drug inhibition can last up to 3 days after gfj intake ceases (Tankanaga 2000a, Tankanga 2000 b).
Different preparations of gfj vary as CYP3A inhibitors. Reconstituted frozen concentrate is generally used in clinical studies, and it is a more potent CYP3A4 inhibitor than fresh gfj because gfj rind (which contains an oil that itself is a potent CYP3A inhibitor) is added to frozen concentrate during processing (Schmiedlin-Ben 1997). White gfj is a more potent inhibitor than pink gfj (Fukuda 2000).
To be significantly effected by gfj, not only must a CYP3A substrate have low bioavailability, but it must have a significant portion metabolized by intestinal CYP3A and/or be a substrate and/or inhibitor of PCP. Conversely, if a known substrate of CYP 3A can be shown be have no significant interaction with gfj, it can be assumed that it is mostly metabolized by hepatic CYPs (e.g., alprazolam Yasui 2000, quinine, Ho 1999). The ability to analyze the relative contributions of liver CYP 3A metabolism, intestinal CYP 3A metabolism and PGP effects to a CYP3A drug-drug interaction is now available by adding gfj as a "knock-out" drug and small bowel biopsy PGP studies to standard bioavailability studies. (Hall 1999).
