Summary
The pharmacokinetics of valpromide, a primary amide of valproic acid, was investigated in 6 healthy, adult male volunteers, each of whom was given 900 mg as a marketed, enteric-coated tablet and a solution. Valpromide was biotransformed to valproic acid after the administration of the tablet and the solution with a bioavailability of 0.79±0.24 and 0.77±0.12, respectively, relative to a marketed tablet of valproic acid. The absorption of valpromide was not rate-limited by dissolution. As a solid, non-hygroscopic, neutral prodrug of valproic acid, valpromide may be a good alternative to valproic acid and sodium valproate.
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References
Favel P, Cartier J, Gratadow JP, Gratadow G (1973) Depamide® in the treatment of epilepsy: a clinical trial. Epilepsia 14: 329–334
Musolino R, Gallitto G, Morgant L, Pisani F, Di Perri R (1980) The antiepileptic properties of n-dipropylacetamide (Depamide®). Acta Neurol 2: 107–114
Pisani F, Di Perri R (1980) Some clinical pharmacological aspects of n-dipropylacetamide. Ital Neurol Sci 4: 245–249
Pisani F, Fazio A, Oteri G, Di Perri R (1981) Dipropylacetic acid plasma levels: diurnal fluctuations during chronic treatment with dipropylacetamide. Ther Drug Monit 3: 297–301
Pisani F, D'Agastano AA, Fazio A, Oteri G, Pimerano G, Di Perri R (1982) Increased dipropylacetic acid bioavailability from dipropylacetic acid by food. Epilepsia 23: 115–121
Reynolds JEF (1982) Martindale — the extra pharmacopoeia, 28th edn., Pharmaceutical Press, London, pp 1250
Schobben F (1983) Valproic acid: pharmacokinetic aspects. Br J Clin Pract 27 [Suppl]: 48–51
Pisani F, Fazio A, Oteri G, Di Perri R (1982) A study on the metabolism of dipropylacetamide to dipropylacetic acid in rats. J Pharm Pharmacol 34: 45–46
Bialer M, Rubinstein A (1983) A comparative study on the pharmacokinetics of valpromide after intravenous administration in dogs. J Pharm Pharmacol 35: 607–609
Bialer M, Rubinstein A (1984) Pharmacokinetics of valpromide in dogs after various modes of administration. Biopharm Drug Dispos 5: 177–183
Bialer M, Friedman M, Rubinstein A (1984) A rapid GLC assay for plasma monitoring of valpromide and valproic acid. J Pharm Sci 73: 991–993
Klotz U, Antonin KH (1977) Pharmacokinetics and bioavailability of sodium valproate. Clin Pharmacol Ther 21: 736–747
Johno I, Huang MY, Levy RH (1982) Systemic interaction between valproic acid and free fatty acids in rhesus monkeys. Epilepsia 23: 649–656
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York, pp 445–449
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York, pp 1–43
Martin BK (1967) Drug urinary excretion data — some aspects concerning the interpretation. Br J Pharmacol Chemother 29: 181–193
Bialer M, Hussein Z, Dubrovsky J, Raz I, Abramsky O (1984) Pharmacokinetics of valproic acid obtained after administration of three oral formulations to humans. Israel J Med Sci 20: 46–50
Schobben F, van der Kleijn E (1982) Valproate biotransformation. In: Woodbury DM, Perry JK, Pippenger CE (eds) Antiepileptic drugs, 2nd edn. Raven Press, New York, pp 567–578
Shafer H, Luhrs R (1978) Metabolite pattern of valproic acid. Arzneimittelforsch 28: 657–662
Bialer M, Hussein Z, Raz I, Abramsky O, Herishanu Y, Pachys F (1984) Pharmacokinetics of valproic acid after single dose administration to healthy subjects. Biopharm Drug Dispos (in press)
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Bialer, M., Rubinstein, A., Raz, I. et al. Pharmacokinetics of valpromide after oral administration of a solution and a tablet to healthy volunteers. Eur J Clin Pharmacol 27, 501–503 (1984). https://doi.org/10.1007/BF00549603
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DOI: https://doi.org/10.1007/BF00549603