© 1991 Oxford University Press
research-article |
Endogenous formation of N-nitrosamines from piperazine and their urinary excretion following antihelmintic treatment with piperazine citrate
Institute of Toxicology and Chemotherapy, German Cancer Research Center Im Neuenheimer Feld 280, D-6900 Heidelberg. FRG
1Department of Pharmaceutical Sciences Srinagar 190006, Jammu and Kashmir, India
2Departmtnt of Biochemistry, University of Kashmir Srinagar 190006, Jammu and Kashmir, India
3Department of Gasteroenterology, SK lnstitute of Medical Sciences Srinagar 190006, Jammu and Kashmir, India
Antihelmintic treatement with piperazine (1,4-diazacyclohexane) for microfilarie parasitism results in the endogenous formation of piperazine-derived N-nitrosamines. Tbe urinary excretion of these N-nitrosamines was determined by biochemical monitoring of 14 patients receiving 2 g piperazine citrate. The urinary excretion (mean ± SD) of N-mononitrosoperazine (MNPz) was 27.0 ± 26.7 µg/day (range 0.6–96.0 µg/day). Trace levels of 0.73 ± 0.92 µg/day N,N'-dinitrosopiperazine (DNPz) (range ND-2.8 µg/day) were also found in 7 of 14 urine samples. N-Nitroso-3-hydroxypyrrolidine (NHPYR), a metabolite of both MNPz and DNPz, was detected in 11 of 14 urine samples at a mean concentration of 1.74 ± 1.72 µg/day (range ND-5.7 µg/day) and traces of N-nitrosodiethanolamine in two samples at levels of 0.3 and <0.1 µg/day. The results show that biochemical monitoring of urinary NHPYR may be a good indicator of endogenous MNPz formation. While DNPz was also detected in urine, conclusive validation for its endogenous formation could not be provided because no evidence was found for the presence of its major metabolite, N-nitroso-(2-hydroxyethyl)glycine in urine.