1.In Vitro and In Vivo Interaction Studies Between Lesinurad, a Selective Urate Reabsorption Inhibitor, and Major Liver or Kidney Transporters.
Shen Z1, Yeh LT2, Wallach K2, Zhu N2, Kerr B2, Gillen M3. Clin Drug Investig. 2016 Mar 7. [Epub ahead of print]
BACKGROUND AND OBJECTIVES: Lesinurad is a selective uric acid reabsorption inhibitor (SURI) under investigation for the treatment of gout. This study elucidated the interaction of lesinurad with major liver and kidney transporters in vitro and evaluated the drug-drug interactions (DDIs) of lesinurad and atorvastatin, metformin, and furosemide in clinical studies.
2.Pharmacokinetics, pharmacodynamics, and safety of lesinurad, a selective uric acid reabsorption inhibitor, in healthy adult males.
Shen Z1, Rowlings C1, Kerr B1, Hingorani V1, Manhard K1, Quart B1, Yeh LT1, Storgard C1. Drug Des Devel Ther. 2015 Jul 2;9:3423-34. doi: 10.2147/DDDT.S85193. eCollection 2015.
Lesinurad is a selective uric acid reabsorption inhibitor under investigation for the treatment of gout. Single and multiple ascending dose studies were conducted to evaluate pharmacokinetics, pharmacodynamics, and safety of lesinurad in healthy males. Lesinurad was administered as an oral solution between 5 mg and 600 mg (single ascending dose; N=34) and as an oral solution or immediate-release capsules once daily (qday) between 100 mg and 400 mg for 10 days under fasted or fed condition (multiple ascending dose; N=32). Following single doses of lesinurad solution, absorption was rapid and exposure (maximum observed plasma concentration and area under the plasma concentration-time curve) increased in a dose-proportional manner. Following multiple qday doses, there was no apparent accumulation of lesinurad. Urinary excretion of unchanged lesinurad was generally between 30% and 40% of dose. Increases in urinary excretion of uric acid and reductions in serum uric acid correlated with dose.
3.Lesinurad: First Global Approval.
Hoy SM1. Drugs. 2016 Mar;76(4):509-16. doi: 10.1007/s40265-016-0550-y.
Lesinurad (ZURAMPIC(®)) is an oral urate-anion exchanger transporter 1 (URAT1) inhibitor developed by Ardea Biosciences (a subsidiary of AstraZeneca) for the treatment of hyperuricaemia associated with gout. It reduces serum uric acid (sUA) levels by inhibiting the function of the transporter proteins (URAT1 and organic anion transporter 4) involved in uric acid reabsorption in the kidney. In December 2015, lesinurad was approved in the USA as combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricaemia associated with gout in patients who have not achieved sUA target levels with a xanthine oxidase inhibitor alone. Lesinurad has also received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for this indication and is in phase III development as a combination therapy in several other countries. This article summarizes the milestones in the development of lesinurad leading to this first approval for hyperuricaemia associated with gout.
4.Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol.
Perez-Ruiz F1, Sundy JS2, Miner JN3, Cravets M4, Storgard C3; RDEA594-203 Study Group. Ann Rheum Dis. 2016 Jan 7. pii: annrheumdis-2015-207919. doi: 10.1136/annrheumdis-2015-207919. [Epub ahead of print]
OBJECTIVES: To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol.