Metabolism of S-nicotine in noninduced and aroclor-induced rats.
The urinary excretion of nicotine and its metabolites in noninduced and Aroclor-induced male and female rats has been determined following intravenous administration of 2'-[14C]-labeled S-nicotine at a dose of 4.6 mumol/kg. Complete recovery of the administered radioactivity was achieved: 95% in urine and 4% in feces over 96 h and 1% remaining in the body. More than 40 nicotine metabolites were found by radio-HPLC; 19 were identified including the cis/trans-diastereomers of nicotine-N'-oxide and 3'-hydroxycotinine. The urinary metabolite profile and excretion kinetics of nicotine and its metabolites were significantly different between noninduced and Aroclor-induced rats. The major urinary nicotine metabolite in the noninduced rat was cis-nicotine-N'-oxide. In the Aroclor-induced rat, cotinine metabolites were the major metabolites found. Sex differences were found for the urinary nicotine metabolite profile, mainly expressed in the excretion of cis-nicotine-N'-oxide, 29% in the male and 17% in the female noninduced rat, and the excretion of cotinine, 5% in the male and 12% in the female noninduced rat. High stereoselectivity was found for the formation of the cis/trans-diastereomers of nicotine-N'-oxide as well as of 3'-hydroxycotinine, the stereoselectivity being more pronounced in male rats.
Schepers
G
G
INBIFO Institut für biologische Forschung, Cologne, Germany.
Rustemeier
K
K
Walk
R A
RA
Hackenberg
U
U
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D002250:Carbon Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D008297:Male; D009538:Nicotine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D001140:Aroclors; D002250:Carbon Radioisotopes; D020111:Chlorodiphenyl (54% Chlorine); D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System