Kinetics of [³H] Trifluoperazine in Bile Fistula Rats

Abstract

1. Anaesthetized male rats with a bile fistula received 12±3 μmol/kg [9-³H] trifluoperazine 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 appeared in bile within 8 h; 80% of the biliary metabolites were unextractable even after β-giucuronidase-arylsulphatase hydrolysis; about 10% were glucuronides of 7-hydroxytrifluo-perazine 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 metabolites remained unchanged