Terminal N-sulphoconjugation of an alicyclic amine (piperazine), identified as a new metabolite of tiaramide in mouse and rat

Abstract

1. A new metabolite of tiaramide, 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazineethanol, found in mouse urine was identified as potassium 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazinesulphonate (M-I).

2. Sex differences in the excretion of M-I were noted in the mouse following oral administration of tiaramide and female mice excreted about 4.6-fold more M-I in urine than males.

3. M-I could not be detected in the urine of male or female rats treated orally with tiaramide. After oral dosing with 1-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-piperazine (DETR), M-I was detected in the urine, and the urinary excretion by male and female rats was similar to that in mice.