The effect of mild and moderate renal impairment on the pharmacokinetics of pridopidine, a new drug for Huntington's disease

Br J Clin Pharmacol. 2016 Feb;81(2):246-55. doi: 10.1111/bcp.12792. Epub 2015 Nov 25.

Abstract

Aim: Pridopidine, a new oral drug for treatment of patients with motor symptoms associated with Huntington's Disease (HD) is currently under development. In steady-state conditions, pridopidine elimination is mediated primarily through renal excretion. This study evaluated single dose and steady-state pharmacokinetics (PK) of a daily dose of pridopidine in subjects with mild and moderate renal impairment and matched healthy subjects.

Methods: Subjects with mild renal impairment (n = 12), moderate impairment (n = 12), or their matched healthy controls (n = 25) participated in this study. Subjects received a single dose of pridopidine (45 mg) on day 1 and a multiple dose cycle of 45 mg once daily on days 5-18. Blood and urine samples were collected on days 1 and 18 for PK analysis.

Results: Mild renal impairment did not affect the PK of pridopidine whilst an increase in exposure was seen in subjects with moderate renal impairment. Subjects with moderate impairment showed reduced plasma clearance (by 44%) and had 68% higher AUC (90% CI 1.22, 2.30) and 26% higher Cmax (90% CI 1.02, 1.56) values than those with normal renal function at steady-state. Pridopidine was safe and well tolerated in healthy subjects and in subjects with mild and moderate renal impairment.

Conclusions: Mild renal impairment has no impact on exposure to pridopidine while moderately impaired renal function resulted in higher pridopidine concentrations.

Keywords: Huntington's disease; pharmacokinetics; pridopidine; renal impairment.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cytochrome P-450 CYP2D6 / genetics
  • Dose-Response Relationship, Drug
  • Female
  • Germany
  • Humans
  • Huntington Disease / complications
  • Huntington Disease / drug therapy*
  • Kidney Diseases* / blood
  • Kidney Diseases* / complications
  • Kidney Diseases* / urine
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Piperidines / blood
  • Piperidines / pharmacokinetics*
  • Piperidines / urine
  • Severity of Illness Index
  • Young Adult

Substances

  • Piperidines
  • Cytochrome P-450 CYP2D6
  • pridopidine