Evaluation of Pharmacokinetic Interactions Between Lesinurad, a New Selective Urate Reabsorption Inhibitor, and Commonly Used Drugs for Gout Treatment

Lesinurad is a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors (XOIs). Open-label pharmacokinetic studies were performed in volunteers or subjects with hyperuricemia (serum uric acid ≥ 8 mg/dL) to investigate interactions of lesinurad (with and without concurrent XOIs) with colchicine and 2 nonsteroidal anti-inflammatory drugs: naproxen and indomethacin. Colchicine studies included consecutive 7-day treatment periods of (1) allopurinol 300 mg, allopurinol 300 mg plus lesinurad 400 or 600 mg, and continued lesinurad 400 or 600 mg; or (2) febuxostat 40 or 80 mg, febuxostat 40 or 80 mg plus lesinurad 400 mg, and continued febuxostat 40 or 80 mg plus lesinurad 600 mg. Naproxen and indomethacin studies included lesinurad 400 mg on day 1, naproxen 250 mg twice daily or indomethacin 25 mg twice daily on days 2-6, and lesinurad 400 mg plus continued naproxen or indomethacin on days 7-13 and the morning of day 14. Lesinurad did not alter the pharmacokinetics of naproxen and modestly altered exposure to colchicine (AUC decrease of ≤ 25%) and indomethacin (AUC increase of ∼35%). Indomethacin did not alter the pharmacokinetics of lesinurad, whereas naproxen modestly decreased the C_max of lesinurad by ∼27%.