title: The effect of mild and moderate renal impairment on the pharmacokinetics of pridopidine, a new drug for Huntington's disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Phase-1 and Clinical Pharmacology, Clinical Development and Medical, Global R&D, Teva Pharmaceuticals, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Rabinovich-Guilatt
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Gruenstadt, Germany.
authors.forename: K E
authors.initials: KE
authors.lastname: Siegler
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Gruenstadt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schultz
authors.affiliation: CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Halabi
authors.affiliation: Formerly NeuroSearch A/S, Denmark and currently Novo Nordisk A/S, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Rembratt
authors.affiliation: Phase-1 and Clinical Pharmacology, Clinical Development and Medical, Global R&D, Teva Pharmaceuticals, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Spiegelstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005858:Germany; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000188:drug therapy*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000652:urine; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D010880:Piperidines; D019389:Cytochrome P-450 CYP2D6; C483720:pridopidine
keywords: Huntington's disease; pharmacokinetics; pridopidine; renal impairment