RT Journal Article
SR Electronic
T1 The formation, disposition, and hepatic metabolism of dimethylnitrosamine in the pig.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 626
OP 631
VO 18
IS 5
A1 G W Harrington
A1 P N Magee
A1 H M Pylypiw, Jr
A1 R Kozeniauskas
A1 R F Bevill
A1 D R Nelson
A1 J C Thurmon
YR 1990
UL http://dmd.aspetjournals.org/content/18/5/626.abstract
AB The disposition, metabolism, and endogenous formation of N-nitrosodimethylamine (NDMA) from nitrosatable precursors was studied in the intact pig and in animals with cannulated hepatic and portal veins and catheterized bile ducts. Rates of disappearance of NDMA from peripheral venous and arterial blood after iv injections were virtually identical and the compound appeared in bile after a lag time of about 1 hr, with a subsequent decline in biliary concentration at about the same rate as in circulating blood. Measurements of NDMA in portal and hepatic vein blood after oral doses of 10, 1.0 and 0.1 mg/kg, respectively, showed progressively greater hepatic extraction with levels in the hepatic vein approaching the limits of detection after the lowest dose. Both halothane and ethanol virtually abolished the hepatic extraction of NDMA, presumably due to their known inhibitory action on its metabolism in the liver. Endogenous formation of NDMA and N-nitrosomorpholine after oral doses of the amines plus nitrite was demonstrated by their detection and measurement in the portal vein blood. Morpholine was nitrosated more effectively than dimethylamine and inhibited the nitrosation of the latter when the two amines were given together. NDMA was found in the portal blood after sequential oral administration of aminopyrine and nitrite, the concentration being considerably greater after fasting for 24 hr than after a 2-hr fast when much food was present in the stomach.