Phenobarbital Metabolism by Hepatocytes Isolated from Rat

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Abstract
In order to test the validity of the use of hepatocytes as an alternative to studies of metabolism in live animals, phenobarbital (PB) was applied at 37 degrees C to isolated rat hepatocytes, which had been previously induced by PB. The metabolites were extracted by ethyl acetate, at various pH, and identified and evaluated by GC-MS. PB was not metabolized to p-hydroxyphenobarbital as is usually the case in living animals, but it was transformed into sulphoconjugated 2-phenyl-gamma-butyrolactone. This pathway, beta-hydroxylation of the ethyl side chain followed by lactonization, previously described as a secondary metabolic pathway occurring during intoxications, was here the only observed biodegradation. These results show that it is not possible to use hepatocytes as an alternative to live animals.