METABOLISM OF TAMSULOSIN IN RAT AND DOG

1. The metabolism of tamsulosin hydrochloride (TMS), a potent alpha(1) -adrenoceptor blocking agent, was studied after a single oral administ ration to rat and dog. 2. Eleven metabolites (1, 2, 3, 4 and their glu curonides, sulphates of 1 and 3, and A-1) were identified from the uri ne and bile of rat and dog administered TMS. 3. Unchanged drug and met abolites in urine and bile were quantified in rat and dog dosed with C -14-TMS (1 mg/kg). In rat the main metabolic routes were de-ethylation of the o-ethoxyphenoxy moiety, demethylation of the methoxy benzenesu lphonamide moiety, and conjugation of the resultant metabolites by glu curonic acid and sulphuric acid. In dog the main pathways were de-ethy lation of the ethoxyphenoxy moiety, conjugation of the deethylated pro duct by sulphuric acid, and oxidative deamination of the side chain. 4 . The organ responsible for the metabolism of TMS in rat was estimated using 9000g supernatants of liver, kidney, small and large intestine homogenate and plasma. The drug was rapidly metabolized in liver but h ardly metabolized in the other organs or plasma.