2
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function.

          Methods

          Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60–89 mL/min; N=8), moderate (eCrCl 30–59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data.

          Results

          Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration–time curve by 34%, 54%–65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects.

          Conclusion

          Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

          Related collections

          Most cited references 8

          • Record: found
          • Abstract: not found
          • Article: not found

          Clinical practice. Gout.

           Tuhina Neogi (2011)
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia.

            The aim of this study was to evaluate the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of lesinurad (selective uric acid reabsorption inhibitor) in combination with febuxostat (xanthine oxidase inhibitor) in patients with gout.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Urate crystal deposition disease and gout – new therapies for an old problem

                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                01 November 2016
                : 10
                : 3555-3562
                Affiliations
                [1 ]AstraZeneca LP, Gaithersburg, MD
                [2 ]Ardea Biosciences, Inc., San Diego, CA, USA
                Author notes
                Correspondence: Michael Gillen, AstraZeneca LP, One MedImmune Way, Gaithersburg, MD 20878, USA, Tel +1 302 885 8144, Email michael.gillen@ 123456astrazeneca.com
                Article
                dddt-10-3555
                10.2147/DDDT.S119944
                5098526
                © 2016 Gillen et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Comments

                Comment on this article