title: Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of orange juice and apple juice on the pharmacokinetics and pharmacodynamics of aliskiren.
  
  
  METHODS
  In a randomized crossover study, 12 healthy volunteers ingested 200 ml of orange juice, apple juice or water three times daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h and plasma renin activity up to 24 h.
  
  
  RESULTS
  Orange and apple juice reduced aliskiren peak plasma concentrations by 80% (95% CI 63%, 89%, P < 0.001) and 84% (95% CI 72%, 91%, P < 0.001), and the area under the plasma aliskiren concentration-time curve (AUC) by 62% (95% CI 47%, 72%, P < 0.001) and 63% (95% CI 46%, 74%, P < 0.001), respectively, but had no significant effect on its elimination half-life or renal clearance. The decreases in aliskiren AUC by orange and apple juice correlated with aliskiren AUC during the water phase (r= 0.98, P < 0.001). Plasma renin activity was 87% and 67% higher at 24 h after aliskiren during the orange juice and apple juice phases, respectively, than during the water phase (P < 0.05).
  
  
  CONCLUSIONS
  Orange juice and apple juice greatly reduce the plasma concentrations and renin-inhibiting effect of aliskiren, probably by inhibiting its OATP2B1-mediated influx in the small intestine. Concomitant intake of aliskiren with orange or apple juice is best avoided.
authors.affiliation: Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Tapaninen
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Niemi
mesh_terms: D000328:Adult; D000577:Amides / Q000097:blood*; D000959:Antihypertensive Agents / Q000097:blood*; D001628:Beverages; D032084:Citrus sinensis; D005260:Female; D018565:Food-Drug Interactions; D005650:Fumarates / Q000097:blood*; D006801:Humans; D008297:Male; D027845:Malus; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000502:physiology; D012083:Renin / Q000097:blood; D055815:Young Adult
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D027361:Organic Anion Transporters; C450859:SLCO2B1 protein, human; C446481:aliskiren; D012083:Renin