Metabolism, Distribution and Excretion of Flupenthixol Decanoate in Dogs and Rats

The metabolism of flupenthixol decanoate administered in viscoleo® by intramuscular or subcutaneous injection has been studied by thin‐layer chromatographic techniques after extraction of urine, faeces and organs from dogs and rats. Since only minute amounts of the compound itself were detected in the organs and a high hydrolytic activity of blood and organs was demonstrated byin vitroexperiments, it was concluded that the compound is hydrolyzed in the organism. The flupenthixol thus formed was found to be metabolized by sulphoxidation and by dealkylation in the side chain following the same pattern as that previously shown for flupenthixol. The neuroleptic effect seen in the pharmacological studies is presumably due to flupenthixol, since this is quantitatively by far the most important substance found in brain extracts. In order to study the depot effect of the preparation, blood levels and excretion were followed after administration of the3H‐labelled compound. These studies indicated, that a sustained release of drug from a depot was obtained. The presence of a relatively limited depot was demonstrated.