Grapefruit juice interactions update#
The FDA consumer update confirmed what users of drugs like statins have known for a long time-you shouldn’t eat grapefruit or drink grapefruit juice if you’re taking any of a number of medications. Rather, the warning was for something that grows naturally in the groves of Florida: the sour, juicy grapefruit.
It wasn’t about counterfeit prescription drugs, an unsafe medicine, or a recalled product. Clin Pharmacol Ther 1999 65:237-44.Last month, the FDA issued an unusual warning. 6',7'-Dihydrobergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Edwards DJ, Fitzsimmons ME, Schuetz EG, Yasuda K, Ducharme MP, Warbasse LH, et al.Drug interactions with grapefruit juice.Grapefruits and drugs: when is statistically significant clinically significant?. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Lundahl J, Regardh CG, Edgar B, Johnsson G.Bailey DG, Malcolm J, Arnold O, Spence JD.Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, et al.Cytochrome P450 interactions: are they clinically relevant? Aust Prescr 2001 24:10-2. Other interactions which may be clinically significant occur with amiodarone, atorvastatin, carbamazepine, felodipine and simvastatin. The clinical significance of increased concentrations of sirolimus and tacrolimus is less clear. Of the many interactions studied only cyclosporin can be definitely said to have a clinically significant interaction. 6 Sweet orange juice does not interact, however, Seville (or bitter) orange juice can inhibit CYP3A4 (although this does not affect cyclosporin 7). 5 There are no useful studies with whole grapefruit. 4Īll interactions studied so far have used grapefruit juice.
2, 3 The inhibition can last up to 24 hours with a maximal effect when the juice is given with the drug or up to four hours before the drug. However, the interactions are not simple competition for substrate metabolism, grapefruit juice acts by selective post-translational down regulation of enzyme expression in the intestinal wall. 1 Grapefruit juice appears to selectively inhibit CYP3A4 in the small intestine. Inhibition of either or both systems can increase the bioavailability of a drug. Pgp and CYP3A4 may therefore act in tandem as a barrier to drugs getting from the gut to the systemic circulation.
Drugs can also be pumped back into the intestinal lumen by a P-glycoprotein (Pgp) transporter. Some drugs are therefore metabolised as they are absorbed by the enterocytes. The CYP3A4 enzyme system is found in the liver and in enterocytes.
Grapefruit juice interactions full#
The full table is available with this article on the Australian Prescriber web site.
I have therefore collated available data to produce a table which may help when assessing the significance and clinical relevance of an interaction. Questions about the interaction of drugs with grapefruit juice have increased.
0 kommentar(er)
