Metabolism of 2-Benzylthio-5-Trifluoromethyl Benzoic Acid (BTBA) by the Rat, Dog and Man

Abstract

1. Benzylthio-5-trifluoromethylbenzoic acid (BTBA) is well absorbed by rat, dog and man. The time course of disappearance from plasma in all three species suggests enterohepatic circulation.

2. The principal excretion product in rat urine has been identified as 2-mercapto-5-trifluoromethylbenzoic acid arising via S-dealkylation.

3. 2-Mercapto-5-trifluoromethylbenzoic acid is also converted to the disulphide metabolite, [2,2′-dithiobis(5-trifluoromethyl)benzoic acid], which is secreted together with BTBA and their glucuronide conjugates in rat bile. Rapid hydrolysis in the intestine results in faecal elimination of largely free BTBA and disulphide metabolite (2,2′-dithiobis[5-trifluoromethyl]benzoic acid).

4. In man, approximately 50% of the dose is recovered from urine as amino-acid and glucuronide conjugates of the drug and its debenzyl metabolite (2-mercapto-5-trifluoromethylbenzoic acid).

5. The drug is not readily metabolized by the dog and is secreted with bile and eliminated unchanged with faeces.