Summary
The pharmacokinetics of the anti-epileptic drug di-n-propylacetate (DepakineR) have been studied in 7 patients, in whom plasma concentrations were determined during and following subchronic treatment. Elimination of the drug appeared to follow a monophasic exponential course; biological half lives were 8 to 15 hours. The data supported the assumption that an open one-compartment model can be used to describe the kinetics of dipropylacetate in man. The drug appeared to have a relatively restricted distribution: calculated relative distribution volumes ranged from 0.15 to 0.40 1/kg. There were large interindividual differences in clearance rate. The therapeutic range was considered to be between 50 and 100 mg/1 plasma. Plasma levels of phenobarbital were markedly raised during treatment with dipropylacetate for an unknown reason. Determination of the plasma concentrations of drugs at accurately fixed times appears to be a reliable method for pharmacotherapeutic monitoring of epileptic patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bergamini, L., Mutani, T., Furlan, P.M., Riccio, A.: Le Dépakine dans le traitement de l'épilepsie essentielle ou idiopathique. Arch. Suisses Neurol. Neurochir. Psych.106 1 (1970)
Burton, B.S.: On the propyl derivates and decomposition products of ethyl acetoacetate. Amer. chem. J.,3 385–395 (1881)
Dubois, D.: Clinical calorimetry. Arch.intern.Med.17 863, (1916).
Eymard, P., Simiand J., Teoule R., Poverelli M., Werbenec J., Broll M.: Etude de la répartition et de la résorption du dipropylacetate de sodium marqué au 14C chez le rat. J.Pharmacol. (Paris)2 359–368 (1971)
Eymard, P., Ferrandez, B., Gautier, C.: Internal report C.R.E.P.-Labaz Grenoble, June 1972: Methode rapide d'analyse quantitative du dipropylacetate de sodium dans le serum ou le plasma. (personal communication) 1972
Ferrandez, B., Gautier, C.: Internal report C.R.E.P.-Labaz Grenoble, June 1972: Evolution de la concentration sanguine du DPA sodium chez le rat traité au DPA soit par voie orale soit par voie intravéneuse. (personal communication) 1972
Godin, Y., Heiner, L., Mark, J., Mandel, P.: Effects of di-n-propylacetate, an anticonvulsive compound, on GABA metabolism. J.Neurochem.16 869–873 (1969)
Kleijn, E. van der, Guelen, P., Pijnappel, H., van Wijk, C., Rijntjes, N.: Pharmacokinetic concept for chronic treatment with anti-epileptics. In: Methods of analysis of anti-epileptic dnugs. Meyer, J.W.A.et al., eds. Excerpta Medica, (Amst.)9 (1973)
Lacolle, J.Y., Baisse, A.: Internal report C.R.E.P.-Labaz Grenoble, July 1972: Evolution du seuil convulsif au cardiazol chez la souris traitée au DPA par voie orale. (personal communication) 1972
Lebreton, S., Carraz G., Beriel, H., Meunier, H.: Propriétés pharmacodynamiques de l'acide n-dipropylacétique. Deuxième memoire sur les propriétés anti-epileptiques. Thérapie19 451–456 (1972)
Matthes, A., Schmutterer, J.: Klinische Erfahrungen mit einem neuen Antiepileptikum: Dipropylessigsäure. Dtsch.med.Wschr.96 63–66 (1972)
Meinardi, H.: Clinical trials of anti-epileptic drugs. Psychiat.Neurol.Neurochir.74 435–483 (1971)
Mutani, R., Fariello, R.: Effetti dell'acido n-dipropylacetico sull'attivà del focus epilettogeno corticale da cobalto. Riv.Path.nerv.ment.89 24 (1968)
Mutani, R., Fariello, R.: Modificationi dell'attività del focus epilettogeno cortico-motorio da allumina indotte dal sale sodico dell'acido n-dipropylacetico. Bull.Soc.Ital.Biol.Sper. 1418–1421 (1969)
Patry, G., Naquet, R.: Action de l'acide dipropylacétique chez le Papio papio photosensible. Canad.J.Physiol.Pharmacol.49 568–572 (1971)
Schobben, F., van der Kleijn, E.: Determination of di-n-propylacetate in plasma by gas liquid chromatography. Pharm.Weekblad109, 1–4 (1974)
Schobben, F., van der Kleijn, E.: Pharmacokinetics of distribution and elimination of di-n-propylacetate in mouse and dog. Pharm.Weekblad109, 33–42 (1974)
Sherwin, A.L., Preston Robb, J.: Ethosuximide; relation of plasma levels to clinical control. In: Antiepileptic Drugs (Woodbury P.M.et al., eds), New York: Raven Press, 443–448 (1972)
Simler, S., Randrianarisoa, H., Lehmann, A., Mandel, P.: Effets du di-n-propylacétate sur les crises audiogènes de la souris. J.Physiol. (Paris)60 suppl. 2, 547 (1968)
Svensmark, O., Buchthal, F.: Diphenylhydantoin and phenobarbital serum levels in children. Amer.J.Dis.Child.108 82–87 (1964)
Swinyard, E.A.: The pharmacology of dipropylacetic acid sodium with special emphasis on its effects on the central nervous system. (personal communication) 1964
Wagner, J.G.: Biopharmaceutics and relevant pharmacokinetics. Hamilton, Illinois: Drug Intelligence Publications 273 (1971)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schobben, F., van der Kleijn, E. & Gabreëls, F.J.M. Pharmacokinetics of di-n-propylacetate in epileptic patients. Eur J Clin Pharmacol 8, 97–105 (1975). https://doi.org/10.1007/BF00561557
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00561557