Petersen D R, Norris K J, Thompson J A
Drug Metab Dispos. 1984 Nov-Dec;12(6):725-31.
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.
给雄性C57BL、DBA和C3H小鼠腹腔注射尼古丁（1.0毫克/毫升）后，研究了尼古丁、可替宁和尼古丁N-氧化物的代谢情况。尼古丁在血液中的半衰期（t1/2）为5.9至6.9分钟。尼古丁的快速消除伴随着代谢物的快速积累；可替宁在血液中的最大浓度（204至364纳克/毫升）在10分钟内达到，尼古丁N-氧化物（C3H小鼠中为23纳克/毫升）在15分钟内达到。可替宁在血液中的t1/2为20.1至39.8分钟，尼古丁N-氧化物为18.4分钟。尼古丁在脑中的t1/2值与血液中的相似，但肝脏中的值略大（6.3至9.2分钟），且品系间差异显著。发现可替宁的t1/2存在较大的品系相关差异；DBA小鼠血液中该代谢物的消除速率仅约为其他品系测定速率的一半。尼古丁N-氧化物在肝脏中的t1/2为12.7至27.3分钟；C57BL大于DBA大于C3H，各品系间差异显著。长期接触香烟烟雾后的反应也观察到了品系相关差异。与对照组相比，C57BL和DBA小鼠中注射尼古丁的t1/2似乎略有降低，但C3H小鼠肝脏中的t1/2增加了60%。
