Kinetics of [3H]trifluoperazine in bile fistula rats

1. Anaesthetized male rats with a bile fistula received 12-3 micron mol/kg [9-3H]tri-fluoperazine into the tail vein, and the biliary excretion of total radioactivity, unchanged drug and phenolic glucuronides was followed for 8 h. 2. About half of the administered radioactivity apeared in bile within 8 h;80% of the biliary metabolites were unextractable even after beta-glucuronidasearylsulphatase hydrolysis; about 10% were glucuronides of 7-hydroxytrifluoperazine and its N-demethylated analogue; approx. 0-6% of the excreted radioactivity was unchanged drug. 3. A more rapid excretion, but a similar metabolite pattern, was observed when the drug was administered into the portal vein and bile was collected for 2 h. 4. Rats pre-treated with trifluoperazine per os for 3 weeks and then given the radioactive dose into the tail vein excreted increased quantities of the demethylated phenol glucuronide, while the other metabolities remained unchanged.