Pharmacokinetics of tobacco-specific N-nitrosamines.
Methods were developed to determine the biological half-life of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in Syrian golden hamsters and Fischer rats. The formation and elimination of 4-(N-nitrosomethylamino)-1-(-3-pyridyl)-1-butanol (NNA1), the major metabolite of NNK, was determined in the context of this study. The method consisted of extraction of the nitrosamine with ethyl acetate, elution through a Clin-Elut column, and concentration of the sample, followed by gas chromatography-thermal energy analysis. Biological half-lives of NNN, NNK and NNA1 in hamsters were found to be 0.77, 0.25 and 1.78 h, respectively; in rats they were 5.78, 1.78 and 3.56 h. These findings clearly indicate species differences in the pharmacokinetics associated with the distribution and elimination of the tobacco-specific N-nitrosamines.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines / Q000378:metabolism*; D010947:Plants, Toxic; D051381:Rats; D011916:Rats, Inbred F344; D014026:Nicotiana
D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine