FORMATION OF N-MONONITROSOPIPERAZINE IN THE STOMACH AND ITS EXCRETION IN THE URINE AFTER ORAL INTAKE OF PIPERAZINE

Piperazine, a secondary amine widely used as an anthelmintic drug, nitrosates rapidly in vitro to form 2 N-nitrosamines. Anhydrous piperazine and a drug formulation had a content of 0.2-20 .mu.g of the suspected carcinogen N-mononitrosopiperazine/g piperazine, but no detectable amounts of the carcinogen N,N''-dinitrosopiperazine. The aim of this study was to investigate the possible nitrosation of the drug piperazine in man. Thirty min after oral administration of 480 mg piperazine to 4 fasting, healthy, male volunteers, gastric juice contained 140-230 .mu.g/l N-mononitrosopiperazine as determined by gas chromatography-thermal energy analysis. The total amount produced by endogenous formation in the stomach was estimated to have been 30-66 .mu.g. N-Mononitrosopiperazine was not detected in blood, but was excreted in the urine, mainly in the first 6 h (0.7-2.1 .mu.g) with half of this appearing within 3 h. Internal acidification of the urine did not affect the excretion or content. N,N''-Dinitrosopiperazine was not found in any sample of gastric juice, blood or urine. The excretion of piperazine was in accordance with earlier findings. Coadministration of 2 g ascorbic acid resulted in a significant but incomplete and varying inhibition of the nitrosation in the stomach and the excretion in urine.