Metabolism of paraldehyde to acetaldehyde by rat liver microsomes.

Paraldehyde (PAL) was shown to be metabolized to acetaldehyde (AcH) by rat liver microsomes in vitro only when the cofactors for the cytochrome P-450 system were present. Microsomes from phenobarbital treated rats significantly increased the amount of AcH produced from PAL. Attempts to inhibit this reaction by addition of SKF-525A to the incubation medium resulted in augmentation of the AcH generated, very likely due to the metabolic deethylation of SKF-525A itself to AcH. Rats pretreated with D-penicillamine and then given PAL excreted 2,5,5-trimethylthiazolidine-4-carboxylic acid (TTCA)-a condensation product of AcH and D-penicillamine-in the urine. These results strongly suggest that PAL is metabolized in vivo by the hepatic microsomal system giving rise to AcH as a metabolite.