Pridopidine is being developed for the treatment of impaired motor function 
associated with Huntington's disease and belongs to a new class of compounds 
known as dopidines, which act as dopaminergic stabilizers. In vitro studies have 
shown that pridopidine is a substrate for the P450 cytochrome 2D6 enzyme 
(CYP2D6), and clinical data show that the half-life of pridopidine is different 
following single dosing versus at steady state. To further investigate the 
pharmacokinetic profile of pridopidine and to establish whether dose adjustment 
is needed in poor CYP2D6 metabolizers, a single-centre, open-label, 
multiple-dose study in healthy volunteers was performed. In total, 24 extensive 
CYP2D6 metabolizers (EMs) and 12 poor CYP2D6 metabolizers (PMs) were enrolled. 
Both groups received 45 mg pridopidine twice daily (b.i.d.). Plasma samples were 
taken during the first day of b.i.d. dosing (Day 1) and at steady state, 
following 14 days of b.i.d. dosing. At Day 1, total exposure in PMs was almost 
three times higher than those in EMs (AUC0-∞ = 11,192 and 3,782 h·ng/mL, 
respectively; PM/EM ratio = 2.96; p < 0.001). However, at steady state, PMs and 
EMs had comparable exposure due to a reduction in pridopidine elimination in EMs 
over time. Thus, at steady-state peak (C max) and total (AUC0-24) exposures were 
only 1.24 and 1.29 times higher, respectively, in PMs than EMs. These results 
support that pridopidine is a CYP2D6 auto-inhibitor. Pridopidine was well 
tolerated in both EMs and PMs. The slightly higher exposure level in PMs at 
steady state does not indicate a need for dose adjustment or genotyping for 
CYP2D6 metabolizer status.