European Journal of Clinical Pharmacology

, Volume 38, Issue 3, pp 289–291 | Cite as

Pharmacokinetics of a valpromide isomer, valnoctamide, in healthy subjects

  • M. Bialer
  • A. Haj-Yehia
  • N. Barzaghi
  • F. Pisani
  • E. Perucca


The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a prodrug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.

Key words

valnoctamide valpromide valproic acid pharmacokinetics healthy subjects tranquiliser 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Stepansky W (1960) A clinical study in the use of valmethamide, an anxiety reducing drug. Curr Ther Res 2: 144–149Google Scholar
  2. 2.
    Reynolds JEF (1982) Martindale — the extra pharmacopea, 28th edn. Pharmaceutical Press, London, p 1563Google Scholar
  3. 3.
    The Merck Index, 10th ed (1983) Merck, Rahway, NJ, USA, pp 9715Google Scholar
  4. 4.
    Chambon JP, Perio A (1980) Valnoctamide: pharmacological data suggesting an antiepileptic activity. Neurosci Lett [Suppl] 5: S327-S327Google Scholar
  5. 5.
    Haj-Yehia A, Bialer M (1988) Pharmacokinetics of a valpromide isomer, valnoctamide, in dogs. J Pharm Sci 77: 831–834Google Scholar
  6. 6.
    Bialer M, Rubinstein A, Raz I, Abramsky O (1984) Pharmacokinetics of valpromide after oral administration of a solution and a tablet to healthy volunteers. Eur J Clin Pharmacol 27: 501–503Google Scholar
  7. 7.
    Bialer M, Rubinstein A, Dubrovsky J, Raz I, Abramsky O (1985) A comparative pharmacokinetic study of valpromide and valproic acid after intravenous administration in humans. Int J Pharm 23: 25–33Google Scholar
  8. 8.
    Pisani F and De Perri R (1980) Some clinical pharmacological aspects of N-dipropylacetamide. Ital J Neurol Sci 4: 245–249Google Scholar
  9. 9.
    Pisani F, Fazio A, Oteri G, Di Perri R (1981) Dipropylacetic acid plasma levels; diurnal fluctuations during chronic treatment with dipropyl-acetamide. Ther Drug Monit 3: 297–301Google Scholar
  10. 10.
    Levy RH (1984) Valproate, modern perspectives. Epilepsia 25 [Suppl 1]Google Scholar
  11. 11.
    Bialer M, Hoch B (1985) Rapid gas chromatographic assay for monitoring valnoctamide. J Chromatogr Biomed Applic 337: 408–411Google Scholar
  12. 12.
    Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd ed. Dekker, New York, pp 445–449Google Scholar
  13. 13.
    Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd ed. Dekker, New York, pp 409–417Google Scholar
  14. 14.
    Yamaoka K, Nakagawa T, Uno T (1978) Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm 6: 574–588Google Scholar
  15. 15.
    Wilkinson GR, Shand DG (1975) A physiological approach to hepatic clearance. Clin Pharmacol Ther 18: 377–390Google Scholar
  16. 16.
    Yamaoka K (1986) “Methods for pharmacokinetic analysis for personal computer”, 2nd edn. Nanko-D Ltd., Tokyo, pp 145–175Google Scholar
  17. 17.
    Haj-Yehia A and Bialer M (1989) Structure pharmacokinetic relationships of a series of valpromide derivatives with antiepileptic activity. Pharm Res 6: 683–687Google Scholar
  18. 18.
    Lambert PA (1984) Acute and prophylactic therapies of patients with affective disorders using valpromide (dipropylacetamide). In: Emrich HM, Okama T, Muller AA (eds) Anticonvulsants in Affective Disorders. Excerpta Medica, Amsterdam, pp 33–44Google Scholar
  19. 19.
    Emrich HM (1987) Anti-Epileptic Agents. II. Diphenylhydantoin, Dipropylacetamide, Valproate and Progabide. In: Johnson FN (ed) Lithium combination treatment. Karger, Basel, pp 156–163Google Scholar
  20. 20.
    Lambert PA, Venaud G (1987) Utilization du valpromide en therapeutique psychiatrique. L' Encéphale 13: 367–373Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • M. Bialer
    • 1
  • A. Haj-Yehia
    • 1
  • N. Barzaghi
    • 2
  • F. Pisani
    • 3
  • E. Perucca
    • 2
  1. 1.Department of Pharmacy, School of PharmacyHebrew UniversityJerusalemIsrael
  2. 2.Institute of Medical PharmacologyUniversity of PaviaPaviaItaly
  3. 3.Department of NeurologyUniversity of MessinaMessinaItaly

Personalised recommendations