PMID: 6111759Dec 1, 1980Paper

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

Neurochemical Research
M I Aly, A A Abdel-Latif

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 the 14C/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 symaptosomal 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 contro...Continue Reading

References

Dec 1, 1976·Epilepsia·J S Lockard, R H Levy
Dec 1, 1968·The Journal of Clinical Investigation·B W Festoff, S H Appel
Mar 1, 1970·Journal of Neurochemistry·A A Abdel-LatifN Hedrick
Sep 1, 1971·The Journal of Clinical Investigation·A V Escueta, S H Appel
Jul 1, 1972·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·K KukinoH Takahira
Mar 20, 1980·The New England Journal of Medicine·J Koch-Weser, T R Browne

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Citations

Jan 1, 1982·Progress in Neurobiology·A ChapmanJ C Vernieres
Aug 11, 1998·Biochemical Pharmacology·A Siafaka-KapadaiM Javors
Oct 24, 2001·European Journal of Medicinal Chemistry·J A PlattsD Butina
May 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G R GrannemanJ W Kesterson
Nov 1, 1988·Kidney International·M Rengel-ArandaJ M Lopez-Novoa
Dec 27, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Maria MavrikakiGeorge Panagis
Nov 26, 2013·Mass Spectrometry Reviews·Christian BerchtoldRenato Zenobi
Oct 1, 1995·European Journal of Clinical Chemistry and Clinical Biochemistry : Journal of the Forum of European Clinical Chemistry Societies·I CepelakA Mandusić
Aug 1, 1990·Neurochemical Research·M NilssonL Rönnbäck

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