Hepatic Secretion and Urinary Excretion of Three S35-Labeled Phenothiazines in the Dog

The present studies indicate that in the dog chlorpromazine, prochlorperazine, and trifluoperazine are rapidly absorbed from the intestine and that there is a rapid hepatic clearance of the phenothiazines. The biliary and urinary excretions of these compounds are greatly affected by the side chain of the phenothiazine nucleus. The “methylpiperazinylpropyl” side chain (prochlorperazine and trifluoperazine) markedly increases the rate of biliary excretion and reduces the urinary excretion of the parent compounds and/or their metabolites compared with the excretion of chlorpromazine and/or its metabolites (dimethylaminopropyl side chain). Moreover, chlorpromazine and/or its metabolites excreted in bile are reabsorbed from the intestine, resulting in an entero-hepatic recirculation.