Benowitz N L, Jacob P, Sachs D P
Clinical Pharmacology Unit, San Francisco General Hospital Medical Center, CA 94110, USA.
Clin Pharmacol Ther. 1995 May;57(5):590-4. doi: 10.1016/0009-9236(95)90044-6.
In most people, nicotine is extensively (70% to 80%) metabolized to cotinine by C-oxidation. In a clinical trial, a 57-year-old woman was found to have the expected plasma levels of nicotine but unusually low plasma levels of cotinine both when smoking cigarettes and while receiving transdermal nicotine. To characterize her metabolism, simultaneous infusions of deuterium-labeled nicotine (d2) and cotinine (d4) were administered, with comparison to 20 other control smokers. The clearance of nicotine was unusually low (6.5 ml/min/kg versus 17.2 ml/min/kg), and the half-life of nicotine significantly longer (348 minutes versus 138 minutes) in the index case subject compared with the control subjects. The clearance of cotinine was normal. The index case subject converted only 9% of nicotine to cotinine, compared with 72% for the control subjects. As far as we know, this is the first person with deficient C-oxidation of nicotine to be characterized. Deficient C-oxidation of nicotine is associated with a long half-life of nicotine and deficient generation of cotinine, both of which could influence the risks and addictiveness of tobacco use in affected individuals.
在大多数人身上，尼古丁通过C氧化作用大量（70%至80%）代谢为可替宁。在一项临床试验中，一名57岁女性在吸烟时以及接受经皮尼古丁治疗时，血浆尼古丁水平符合预期，但血浆可替宁水平异常低。为了表征她的代谢情况，给她同时输注氘标记的尼古丁（d2）和可替宁（d4），并与其他20名对照吸烟者进行比较。与对照受试者相比，该病例受试者的尼古丁清除率异常低（6.5毫升/分钟/千克，而对照为17.2毫升/分钟/千克），尼古丁半衰期显著延长（348分钟，而对照为138分钟）。可替宁的清除率正常。该病例受试者仅将9%的尼古丁转化为可替宁，而对照受试者为72%。据我们所知，这是首例被表征为尼古丁C氧化作用缺陷的人。尼古丁C氧化作用缺陷与尼古丁的长半衰期以及可替宁生成不足有关，这两者都可能影响受影响个体使用烟草的风险和成瘾性。
