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

• Published in: British journal of clinical pharmacology 2016-02, Vol.81 (2), p.246-255
• Main Authors: Rabinovich‐Guilatt, L., Siegler, K. E., Schultz, A., Halabi, A., Rembratt, A., Spiegelstein, O.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Clinical Trials; Cytochrome P-450 CYP2D6 - genetics; Dose-Response Relationship, Drug; Female; Germany; Humans; Huntington Disease - complications; Huntington Disease - drug therapy; Huntington's disease; Kidney Diseases - blood; Kidney Diseases - complications; Kidney Diseases - urine; Kidney Function Tests; Male; Middle Aged; pharmacokinetics; Piperidines - blood; Piperidines - pharmacokinetics; Piperidines - urine; pridopidine; renal impairment; Severity of Illness Index; Young Adult
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12792

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.