Reinsberger Claus, Dorn Thomas, Krämer Günter
Swiss Epilepsy Center, Bleulerstr. 60, 8008 Zurich, Switzerland.
Seizure. 2008 Oct;17(7):651-3. doi: 10.1016/j.seizure.2008.05.009. Epub 2008 Jun 25.
The influence of smoking on lamotrigine (LTG) serum levels in 44 patients with epilepsy treated with LTG in monotherapy was examined. Fifteen patients were smokers (range: three cigarettes per month -- three packages per day) and 29 were non-smokers. Analyzing 204 samples, smokers had a significantly lower serum level-to-dose ratio than non-smokers (0.0657mmolmg/l (smokers) vs. 0.0785mmolmg/l (non-smokers)) (p=0.0014). Analyzing only male patients, the same relationship with an almost equally high level of significance could be demonstrated (p=0.008). Our data indicate that the demonstrated effect of smoking on LTG metabolism is likely to be mediated via UDPGT2B7, as LTG is not a substrate of cytochrome P450 isoenzymes and UDPGT1A4 activity may not be affected by nicotine, but the exact mechanism underlying the demonstrated effect remains uncertain. These findings are likely to be independent from hormonal changes, as they could also be reproduced in the group of male patients. Therefore, the effect of smoking on blood levels of LTG has to be taken into account in the evaluation of treatment with this drug.
我们研究了吸烟对44例接受拉莫三嗪（LTG）单药治疗的癫痫患者血清LTG水平的影响。15例患者为吸烟者（范围：每月3支香烟 - 每天3包），29例为非吸烟者。在分析的204份样本中，吸烟者的血清水平与剂量比显著低于非吸烟者（0.0657mmolmg/l（吸烟者）对0.0785mmolmg/l（非吸烟者））（p = 0.0014）。仅分析男性患者时，也可显示出相同的关系，且显著性水平几乎相同（p = 0.008）。我们的数据表明，吸烟对LTG代谢的影响可能是通过UDPGT2B7介导的，因为LTG不是细胞色素P450同工酶的底物，且UDPGT1A4活性可能不受尼古丁影响，但所显示效应的具体机制仍不确定。这些发现可能与激素变化无关，因为在男性患者组中也可重现。因此，在评估该药物治疗时，必须考虑吸烟对LTG血药浓度的影响。
