Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren

center dot Aliskiren is an antihypertensive drug with a low oral bioavailability. center dot Aliskiren is eliminated primarily unchanged into bile, and it is a substrate of the organic anion transporting polypeptide 2B1 (OATP2B1) influx transporter, the P-glycoprotein efflux transporter and cytochrome P450 3A4. center dot Flavonoids in orange and apple juice have been shown to inhibit OATP2B1 in vitro. WHAT THIS STUDY ADDS center dot Orange juice and apple juice markedly reduce the plasma concentrations of aliskiren probably by inhibiting its OATP2B1-mediated intestinal absorption. center dot Concomitant intake of aliskiren with orange or apple juice is best avoided. AIM 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.