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Studies on distribution and metabolism of valproate in rat brain, liver, and kidney

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Abstract

Time-course studies on the distribution and metabolism of valproate (VPA) in rat brain, liver, and kidney, after intraperitoneal injection of a mixture of [14C]VPA and [3H]VPA, showed that: (1) maximal amount of radioactivity in the various tissues was observed after 30 min from the time the drug was administered; (2) at 30 min the distribution of labeled VPA in brain, liver, and kidney was 17%, 64%, and 19% of the total radioactivity, respectively; (3) at 24 hr more than 97% of the total radioactivity was lost from the tissues and the14C/3H ratios increased significantly with time. Studies on the regional distribution of the drug showed that it is relatively homogeneously distributed. Studies on the subcellular distribution of the drug showed that it is associated mostly with the soluble and mitochondrial fractions, with little radioactivity in the myelin and synaptosomal fractions. Radiochromatography of VPA metabolites in perchloric acid extracts from brain, liver, and kidney revealed the presence of four metabolites. VPA was not incorporated into phospholipids of the neuronal membranes. Furthermore, it had no significant effects on Mg2+-ATPase and (Na++K+)-ATPase in synaptosomes and microsomes obtained either from control or from rats injected with VPA. It was concluded that this antiepileptic drug does not appear to act through its incorporation into neuronal membrane or through its action on the Na+ pump.

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References

  1. Simon, D., andPenry, J. K. 1975. Sodium di-N-propylacetate in the treatment of epilepsy. Epilepsia 16:549–573.

    Google Scholar 

  2. Abdel-Latif, A. A. 1973. Na+-K+-ATPase and ion transport in synaptosomes. Pages 145–188,in Fried, R. (ed.), Methods in Neurochemistry, Vol. V, Marcel Dekker, New York.

    Google Scholar 

  3. Abdel-Latif, A. A., Akhtar, R. A., andHawthorne, J. N. 1977. Acetylcholine increases the breakdown of triphosphoinositide of rabbit iris muscle prelabelled with32P phosphate. Biochem. J. 162:61–73.

    Google Scholar 

  4. Abdel-Latif, A. A., Smith, J., andHedrick, N., 1970. Na+-K+-ATPase and nucleotide metabolism in synaptosomes of rat brain. J. Neurochem. 17:391–401.

    Google Scholar 

  5. Gomori, G. 1942. A modification of the colorimetric phosphorus determination for use with the photoelectric colorimeter. J. Lab. Clin. Med. 27:955–960.

    Google Scholar 

  6. Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  7. Eymard, P., Simiand, J., Teoule, R., Polverelli, M., Werbenec, J. P., andBroll, M. 1971. Etude de la repartition et de la resorption du dipropyl acetate de sodium margue au14C chez le rat. J. Pharmacol. 2:359–368.

    Google Scholar 

  8. Kukino, K., Mineura, L., Deguchi, T., Ishii, A., andTakahira, H. 1972. Studies on a new anticonvulsant drug, sodium dipropylacetate. Assay for metabolites and metabolic pathway. J. Pharm. Soc. Jpn. 92:896–900.

    Google Scholar 

  9. Kuhara, T., andMatsumoto, I. 1974. Metabolism of branched medium chain length fatty acid. I. ω-Oxidation of sodium dipropylacetate in rats. Biomed. Mass Spectrom. 1:291–294.

    Google Scholar 

  10. Kochen, W., Imbeck, H., andJakobs, C. 1977. Untersuchungen über die ausscheidung von metaboliten der valproinsäure in urin der ratte und des menschen. Arznein. Forsch. 27:1090–1099.

    Google Scholar 

  11. Matsumoto, I., Kuhara, T., andYoshino, M. 1976. Metabolism of branched medium chain length fatty acid. II. β-Oxidation of sodium dipropylacetate in rats. Biomed. Mass Spectrom. 3:235–240.

    Google Scholar 

  12. Lockard, J. S., andLevy, R. H. 1976. Valproic acid: Reversibly acting drug? Epilepsia 17:477–479.

    Google Scholar 

  13. Kupferberg, H. J. 1980. Sodium valproate. Pages 643–654,in Glaser, G. H., Penry, J. K., andWoodbury, D. M. (eds.), Antiepileptic Drugs: Mechanism of Action, Raven Press, New York.

    Google Scholar 

  14. Woodbury, D. M. 1955. Effect of diphenylhydantoin on electrolytes and radiosodium turnover in brain and other tissue of normal, hyponatremic and postical rats. J. Pharmacol. Exp. Ther. 115:74–95.

    Google Scholar 

  15. Festoff, B. W., andAppel, S. H. 1968. Effect of diphenylhydantoin on synaptosome Na+-K+-ATPase. J. Clin. Invest. 47:2752–2758.

    Google Scholar 

  16. Escueta, A. V., andAppel, S. H. 1971. Diphenylhydantoin and K+ transport in isolated nerve terminals. J. Clin. Invest. 50:1977–1984.

    Google Scholar 

  17. Lewin, E., andBleck, V. 1971. The effect of phenytoin administration on Na+-K+-ATPase in cortex. Neurology 21:647–651.

    Google Scholar 

  18. Rawson, M. D., andPincus, J. H. 1968. The effect of diphenylhydantoin on Na+-K+-ATPase in microsomal fractions of rat and guinea pig brain and on whole homogenates of human brain.Biochem. Pharmacol. 17:573–579.

    Google Scholar 

  19. Swanson, P. D., andCrane, P. O. 1972. Diphenylhydantoin and movement of radioactive sodium into electrically stimulated cerebral slices.Biochem. Pharmacol. 21:2899–2905.

    Google Scholar 

  20. Browne, T. R. 1980. Valproic acid. New Engl. J. Med. 302:661–666.

    Google Scholar 

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Medical College of Georgia, 30912, Augusta, Georgia

    M. I. Aly & A. A. Abdel-Latif

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  1. M. I. Aly
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  2. A. A. Abdel-Latif
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Contribution No. 0601 from the Department of Cell and Molecular Biology, the Medical College of Georgia, Augusta, Georgia 30912.

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Aly, M.I., Abdel-Latif, A.A. Studies on distribution and metabolism of valproate in rat brain, liver, and kidney. Neurochem Res 5, 1231–1242 (1980). https://doi.org/10.1007/BF00964959

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