Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren.
In a randomized crossover study, 11 healthy volunteers ingested 200 ml of grapefruit juice or water three times a day for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Grapefruit juice reduced aliskiren peak plasma concentration (C(max)) by 81% (range, 42-91%, P < 0.001), area under the plasma aliskiren concentration-time curve (AUC)(0-infinity) by 61% (range, 15-72%, P < 0.001), and elimination half-life (t(1/2)) from 26.1 to 23.6 h (P = 0.020). Therefore, concomitant use of aliskiren and grapefruit juice is best avoided.
Tapaninen
T
T
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Neuvonen
P J
PJ
Niemi
M
M
D000328:Adult; D000577:Amides / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D005260:Female; D018565:Food-Drug Interactions; D005650:Fumarates / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors*; D055815:Young Adult; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D005650:Fumarates; D027361:Organic Anion Transporters; D000092502:Renin Inhibitors; C450859:SLCO2B1 protein, human; C446481:aliskiren; C510163:CYP3A4 protein, human