Summary
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.
Similar content being viewed by others
References
Boxenbaum HG, Riegelman S, Elashoff RM (1974) Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm 2: 123–148
Bross A, Chopard-dit-Jean LH, Schnider O (1958) Synthesever-such in der Emetin-Reihe. 2-hydroxyhydrobenzo(a)chinolizine. Helv Chim Acta 41: 1793–1806
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York, pp 409–417
Jankovic J (1982) Treatment of hyperkinetic movement disorders with tetrabenazine: a double-blind crossover study. Ann Neurol 11: 41–47
Kingston D (1979) Tetrabenazine for involuntary movement disorders. Med J Aust 1: 628–630
McLellan DL, Chalmers RJ, Johnson RH (1974) A double blind trial of tetrabenazine, thiopropazate, and placebo in patients with chorea. Lancet 1: 104–107
Pletscher A, Brossi A, Gey KF (1962) Benzoquinolizine derivatives: A new class of monamine decreasing drugs with psychotropic action. Int Rev Neurobiol 4: 275–306
Quinn PP, Shore PA, Brodie BB (1959) Biochemical and pharmacological studies of RO 1-9569 (tetrabenazine), a non-indole tranquilizing agent with reserpine-like effects. J Pharmacol Exp Ther 127: 103–109
Roberts MS, Watson HM, McLean S, Millingen KS (1981) Determination of therapeutic plasma concentrations of tetrabenazine and an active metabolite by high-performance liquid chromatography. J Chromatogr Biomed Applic 226: 175–182
Rowland M, Tozer N (1980) Clinical pharmacokinetics. Concepts and applications. Lea & Febiger. Philadelphia, pp 119, 128
Schwartz DE, Bruderer H, Rieder J, Brossi A (1966) Metabolic studies of tetrabenazine, a psychotropic drug in animals and man. Biochem Pharmacol 15: 645–655
Schwartz DE, Rieder J (1961) Micromethode de dosage spectro-fluorometrique des benzoquinolizines dans les liquides et tissus biologiques. Clin Chim Acta 6: 453–463
Stumpf W, Graul EH, Hundeshagen H (1961) Experimentelle Untersuchungen zur Pharmakologie des mit3H-markierten tetrabenazines. Arzneimittelforsch 11: 47–49
Toglia JU, McGlamery M, Sambandham RR (1978) Tetrabenazine in the treatment of Huntington's chorea and other hyperkinetic movement disorders. J Clin Psychiatr 39: 81–87
Veng Pedersen PV (1977) Curve fitting and modelling in pharmacokinetics and some practical experiences with NONLIN and a new program FUNFIT. J Pharmacokinet Biopharm 5: 513–531
Wagner JG (1976) Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data. J Pharm Biopharm 4: 443–467
Ward RM, Singh S, Mirkin BL (1980) Fetal clinical pharmacology. In: Avery GS (ed) Drug treatment. Adis, Sydney, New York
Weiss M (1983) Use of gamma distributed residence times in pharmacokinetics. Eur J Clin Pharmacol 25: 695–702
Welch RM, Findlay JWA (1981) Excretion of drugs in human breast milk. Drug Metab Rev 12: 261–277
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Roberts, M.S., McLean, S., Millingen, K.S. et al. The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders. Eur J Clin Pharmacol 29, 703–708 (1986). https://doi.org/10.1007/BF00615962
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00615962