Premium
Pomelo juice but not cranberry juice affects the disposition of cyclosporine in humans
Author(s) -
Fradette C.,
Grenier J.,
Morelli G.,
Merritt J.,
Vranderick M.,
Ducharme M. P.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.196
Subject(s) - grapefruit juice , cranberry juice , bioavailability , cyp3a , crossover study , chemistry , pharmacology , pharmacokinetics , disposition , fruit juice , food science , metabolism , medicine , biochemistry , psychology , social psychology , alternative medicine , urinary system , cytochrome p450 , pathology , placebo
Background Cyclosporine is a CYP3A and PgP susbstrate and coadministration with grapefruit juice increases its biovailability. It is unknown at this time if pomelo, a closely related citrus fruit, interacts with cyclosporine in humans. In addition, a case study reports that cranberry juice interacts with warfarin. Cranberry juice has become a very popular beverage, therefore its effect on cyclosporine disposition needs also to be studied. Methods In an open‐label, randomized, 3‐way crossover design with washouts of 14 days, 12 healthy volunteers received single oral 200 mg doses of cyclosporine with either 240 ml of pomelo juice, cranberry juice, or water under fasting conditions. Multiple whole blood samples were collected up to 36 hours after each dose. Concentrations were determined using a liquid chromatography tandem mass spectrometry method. Results Pomelo juice increased the total exposure (AUC) of cyclosporine by 20% (P<0.0001) and its peak concentration 12% (P<0.01). On the other hand, cranberry juice had no significant effect on the overall disposition of cyclosporine. Conclusion These results suggest that pomelo juice increases the bioavailability of cyclosporine, possibly by inhibiting CYP3A and/or PgP activity in the gut wall. However, drinking cranberry juice does not appear to influence the disposition of cyclosporine and therefore probably does not affect CYP3A and/or PgP activity in the gut wall. Clinical Pharmacology & Therapeutics (2005) 77 , P80–P80; doi: 10.1016/j.clpt.2004.12.196