A comparative study of the disposition of nicotine and its metabolites in three inbred strains of mice.

The disposition of nicotine, cotinine, and nicotine N-oxide was investigated in male C57BL, DBA, and C3H mice following an ip injection of nicotine (1.0 mg/ml). The half-lives (t1/2) of nicotine in blood were 5.9 to 6.9 min. The rapid elimination of nicotine was accompanied by a rapid accumulation of metabolites; maximal concentrations of cotinine in blood (204 to 364 ng/ml) were achieved in 10 min and nicotine N-oxide (23 ng/ml in C3H mice) in 15 min. The t1/2 in blood was 20.1 to 39.8 min for cotinine and 18.4 min for nicotine N-oxide. The t1/2 values for nicotine in brain were similar to those in blood, but the values for liver were slightly larger (6.3 to 9.2 min) and interstrain differences were significant. A large strain-related difference in the t1/2 for cotinine was found; the metabolite was eliminated from the blood of DBA mice at only about one-half the rate determined for the other strains. The t1/2 for nicotine N-oxide in liver ranged from 12.7 to 27.3 min; the values were significantly different with C57BL greater than DBA greater than C3H. Strain-related differences were also observed in response to chronic exposure to cigarette smoke. The t1/2 of injected nicotine appeared to be slightly decreased in C57BL and DBA mice but was increased by 60% in livers of C3H mice compared to a control group.