The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders.

The pharmacokinetics of tetrabenazine and a metabolite, hydroxytetrabenazine, have been investigated in seven patients being treated for involuntary movement disorders. Tetrabenazine had a very low oral systemic availability (mean 0.049 +/- 0.032 SD). First-pass metabolism to hydroxytetrabenazine was extensive, and the systemic availability for this metabolite was high (mean 0.81 +/- 0.30 SD). Since hydroxytetrabenazine has been reported to be as active as tetrabenazine in depleting brain amines, and is present at much higher plasma concentrations than the parent drug, it is likely that this metabolite is the more important therapeutic moiety.