Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine.
Nicotine metabolic profile in man: comparison of cigarette smoking and transdermal nicotine.
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发表时间：
1994
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通讯作者：
N. Benowitz;P. Jacob;I. Fong;Suneel K. Gupta
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作者：
N. Benowitz;P. Jacob;I. Fong;Suneel K. Gupta
本研究的目的是：1）定量评估人体暴露于尼古丁的各种代谢物，2）检查吸入与经皮给药对尼古丁代谢模式的影响，3）评估尼古丁作为各种代谢物在已测量尼古丁全身摄入量的人群中的回收程度。12名吸烟者在吸烟和接受尼古丁透皮吸收时进行了研究。在稳态条件下测量尼古丁及其8种代谢产物的尿排泄。使用血浆浓度和静脉内清除数据确定这些受试者中尼古丁的全身摄入量，因此可以计算以各种代谢物形式排泄的尼古丁占其每日剂量的百分比。研究的主要发现如下：1）高比例尼古丁及其代谢物的测量值可以解释尼古丁全身剂量的（平均88%）; 2）吸入或经皮吸收尼古丁时，代谢模式通常相似; 3）尽管代谢模式存在相当大的个体间差异，但个体的模式是一致的;和4）在个体内，尼古丁和可替宁的结合程度高度相关，但两者都不与3 '-羟基可替宁的结合程度相关。这表明尼古丁和可替宁的结合中涉及相似的酶，而3 '-羟基可替宁的结合中可能涉及不同的酶。
The objectives of this study were to 1) quantitatively assess human exposure to various metabolites of nicotine, 2) examine the influence of inhalation vs. transdermal administration on the patterns of nicotine metabolism, and 3) assess the extent of recovery of nicotine as various metabolites in people whose systemic intake of nicotine has been measured. Twelve smokers were studied while smoking cigarettes and while receiving transdermal nicotine. Urinary excretion of nicotine and eight of its metabolites was measured under steady state conditions. The systemic intake of nicotine in these subjects was determined using plasma concentrations and intravenous clearance data, so the percentage of their daily dose of nicotine excreted as various metabolites could be computed. The major findings of the study are as follows: 1) a high percentage (averaging 88%) of a systemic dose of nicotine can be accounted for by measurement of nicotine and its metabolites; 2) the pattern of metabolism is generally similar when nicotine is inhaled or absorbed transdermally; 3) while there is considerable interindividual variability in the pattern of metabolism, the pattern is consistent for an individual; and 4) within individuals, the extent of conjugation of nicotine and cotinine is highly correlated, but neither is correlated with the extent of conjugation of 3'-hydroxycotinine. This suggests that similar enzymes are involved in the conjugation of nicotine and cotinine, and that a different enzyme may be involved in the conjugation of 3'-hydroxycotinine.