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Formation of N-mononitrosopiperazine in the stomach and its excretion in the urine after oral intake of piperazine.

Abstract：

:Piperazine, a secondary amine widely used as an anthelmintic drug, nitrosates rapidly in vitro to form two N-nitrosamines. Anhydrous piperazine and a drug formulation were found to have a content of 0.2 to 20 micrograms of the suspected carcinogen N-mononitrosopiperazine per gram 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 minutes after oral administration of 480 mg piperazine to four fasting, healthy, male volunteers, gastric juice contained 140 to 230 micrograms/liter N-mononitrosopiperazine as determined by gas chromatography-thermal energy analysis. The total amount produced by endogenous formation in the stomach is estimated to have been 30 to 66 micrograms. N-Mononitrosopiperazine was not detected in blood, but was excreted in the urine, mainly in the first 6 hr (0.07 to 2.1 micrograms) with half of this appearing within 3 hr. 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 both the nitrosation in the stomach and the excretion in urine.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Bellander T,Osterdahl BG,Hagmar L

doi

10.1016/0041-008x(85)90075-4

subject

Has Abstract

pub_date

1985-09-15 00:00:00

pages

193-8

issue

2

eissn

0041-008X

issn

1096-0333

pii

0041-008X(85)90075-4

journal_volume

80

pub_type

杂志文章

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