Valbenazine tosylate (NBI-98854) is the tosylate salt of valbenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor with a Ki value of 150 nM while displaying no significant binding to VAMT1(Ki<10 μM).
Valbenazine is a potent, selective, and specific inhibitor of VMAT2 with no inhibition of the related VMAT1 transporter and minimal off-target interactions at more than 80 other receptor transporters and ion channels[2].
Valbenazine is a novel and highly selective VMAT2 inhibitor that is rapidly absorbed but more slowly metabolized, with a half-life of approximately 20 h that supports once-daily dosing[2]. Valbenazine has moderate absorption with an absolute oral bioavailability of approximately 49%; time to maximum concentration ranges from 0.5 to 1.0 hour. Valbenazine can be taken with or without food. Valbenazine exhibits protein binding of 99%. Valbenazine is primarily metabolized via the hydrolysis of the valine ester and cytochrome P450 (CYP) 3A4/5 into R,R,R-HTBZ and a mono-oxy metabolite[3].
[1] Citrome L. Expert Rev Neurother. 2018, 18(4):323-332. [2] Grigoriadis DE, et al. J Pharmacol Exp Ther. 2017, 361(3):454-461. [3] Stepan Uhlyar, et al. P T. 2018, 43(6): 328-331.