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Metabolism of S-nicotine in noninduced and aroclor-induced rats

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Summary

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 μmol/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 thecis/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 wascis-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 ofcis-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 thecis/trans-diastereomers of nicotine-N′-oxide as well as of 3′-hydroxycotinine, the stereoselectivity being more pronounced in male rats.

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  1. INBIFO Institut für biologische Forschung, Fuggerstr. 3, D-51149, Köln, Germany

    G. Schepers, K. Rustemeier, R. -A. Walk & U. Hackenberg

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  1. G. Schepers
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  2. K. Rustemeier
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  3. R. -A. Walk
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  4. U. Hackenberg
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Schepers, G., Rustemeier, K., Walk, R.A. et al. Metabolism of S-nicotine in noninduced and aroclor-induced rats. Eur. J. Drug Metab. Pharmacokinet. 18, 187–197 (1993). https://doi.org/10.1007/BF03188795

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