Lipid-Induced Changes of Pentobarbital Distribution and Metabolism

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Abstract
The feeding of the naturally occurring lipid compound palmitoylethanol amide to mice for 12 days resulted in a marked prolongation of pentobarbital hypnosis. Analysis of 14C-pentobarbital levels in blood and tissues of PEA-treated animals has shown a lower level of radioactivity in blood and higher activity in tissues after 15 min which indicates that PEA influences the blood/tissue distribution of barbiturate. Determination of 14C-pentobarbital metabolites has revealed that the metabolism of pentbbarbital in liver is decreased. The prolongation of pentobarbital hypnosis in PEA-treated mice may be explained on the basis of higher levels of pentobarbital in brain.Microsomal fatty acid analysis in PEA-treated mice demonstrated a marked change in the composition of fatty acids which suggested that there may be a relationship between microsomal fatty acid composition and drug metabolism.

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