Nicotine metabolism and elimination kinetics in newborns

OBJECTIVE: To characterize the presence of and elimination kinetics of nicotine and its metabolites in newborns. METHODS: Blood samples from 13 newborns were collected during the first day of life and analyzed for nicotine and cotinine. Single daily urine samples were collected from nine newborns for up to 7 days and analyzed by gas chromatography-mass spectrometry for nicotine, cotinine, 3'-hydroxycotinine, and their conjugates. NONMEM was used to determine population half-life values. RESULTS: Blood and urine data gave similar results for nicotine and cotinine elimination kinetics. The elimination half-life for nicotine was 11.2 hours (95% confidence interval CI], 8.0 to 18.9) based on blood data and 9.0 hours (95% CI, 7.0 to 12.4) based on urine data. The elimination half-life for cotinine was 16.3 hours (95% CI, 12.4 to 23.9) based on blood data and was 22.8 hours (95% CI, 19.5 to 25.8) based on urine data. The elimination half-lives for the other metabolites were 13 hours for conjugated nicotine; 19.8 hours for conjugated cotinine; 18.8 hours for 3'-hydroxycotinine; and 19.4 hours for conjugated 3'-hydroxycotinine. The half-life of nicotine is three to four times longer in newborns than in adults, whereas the half-life of cotinine is similar in newborns and adults. CONCLUSIONS: In adults, CYP2A6 is the predominant enzyme responsible for the metabolism of both nicotine and cotinine. The prolonged elimination of nicotine but not of cotinine in the newborn compared with that in the adult may be a result of different newborn CYP2A6 enzymatic substrate specificity, low CYP2A6 activity with another enzyme that is primarily responsible for cotinine metabolism, or differences in tissue distribution.