Urinary metabolite profile of tiaramide in man and in some animal species

Abstract

1. The metabolism of tiaramide, 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazineethanol, was studied in healthy male volunteers and experimental animals.

2. Tiaramide was extensively metabolized in human with only 1.5% excreted unchanged.

3. Urinary metabolites were identified by FD, CI and EI mass spectral comparison with authentic standards. The major urinary metabolites in human were 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazineacetic acid (TRAA), 4-[(5-chloro-2-oxo-3(2H)-benzothiazolyl)acetyl]-1-piperazineacetic acid 1-oxide (TRAO) and the O-glucuronide of tiaramide.

4. TRAO, a new metabolite identified in human urine, was also present in mouse, rat, guinea-pig and monkey, but in smaller amounts than for human.

5. Sex differences in the excretion of sulphate of tiaramide were noted only in the rat.