An osmotic explanation for valproic acid induced choleresis in the rat, dog and monkey

R. G. Dickinson, R. C. Harland, S. N. Kaufman, R. K. Lynn, N. Gerber

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


I.v. administration of sodium valproate (NaVPA), the sodium salt of 2-n-propylpentanoic acid (valproic acid, VPA, Depakene®), to rats and dogs caused an immediate stimulation of bile flow, the magnitude and duration of which was dependent on the dose. In rats given 14C-erythritol, a linear relationship between biliary clearance of erythritol and bile flow indicated that the choleresis was canalicular, rather than ductular, in origin. Increased bile flow was not mediated through an enhanced output of bile acids. Bile produced during choleresis was lower in choleride and bicarbonate concentrations than equivalent bile from control rats given only saline i.v. This anion gap was more than compensated by the amount of VPA-glucuronide (anionic at physiological pH values) in the bile. A close linear relationship existed between the volume of additional bile produced and the amount of conjugated VPA excreted in the bile. The results support the hypothesis that VPA induces choleresis by the osmotic effects of transport of its metabolites across the canalicular membrane.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalArzneimittel-Forschung/Drug Research
Issue number3
StatePublished - 1982

ASJC Scopus subject areas

  • Drug Discovery


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