aliskiren and naringin

To conduct a mechanistic investigation of the interaction between aliskiren and grapefruit juice in healthy subjects.. Twenty-eight subjects received an oral dose of aliskiren 300 mg (highest recommended clinical dose) with 300 mL of either water or grapefruit juice in a two-way crossover design. Safety and pharmacokinetic analyses were performed. In vitro studies were performed in HEK293 cells to investigate the role of organic anion transporting polypeptide (OATP) transporter-mediated uptake of aliskiren.. Co-administration of a single dose of aliskiren with grapefruit juice decreased the plasma concentration of aliskiren, with mean decreases in the AUC(inf), AUC(last), and C(max) of 38, 37, and 61%, respectively. The uptake of [¹⁴C]aliskiren into OATP2B1-expressing cells was essentially the same as that into control cells, and the inhibitor combination atorvastatin and rifamycin had no effect on [¹⁴C]aliskiren accumulation in either cell type. The uptake of [¹⁴C]aliskiren and [³H]fexofenadine was linear in OATP1A2-expressing cells and was reduced by naringin, with IC₅₀ values of 75.5 ± 11.6 and 24.2 ± 2.0 μM, respectively.. Grapefruit juice decreases exposure of aliskiren partially via inhibition of intestinal OATP1A2.

Topics: Adult; Amides; Antihypertensive Agents; Beverages; Biological Transport; Citrus paradisi; Cross-Over Studies; Flavanones; Food-Drug Interactions; Fruit; Fumarates; Half-Life; HEK293 Cells; Humans; Intestinal Mucosa; Male; Organic Anion Transporters; Recombinant Proteins; Renin; Terfenadine; Young Adult