Kyaw Win Thiri, Nagai Masahiro, Kaneta Mika, Kubo Madoka, Nishikawa Noriko, Tsujii Tomoaki, Iwaki Hirotaka, Nomoto Masahiro
Department of Neurology and Therapeutic Medicine, Ehime University Hospital and Graduate School of Medicine, Shitsukawa, Tohon, Ehime, Japan.
Clin Neuropharmacol. 2013 Mar-Apr;36(2):46-51. doi: 10.1097/WNF.0b013e31827fd9cd.
Some patients with Parkinson disease improved their symptoms on treatment with nicotine patch or gum. Nicotine has also been studied for its antidyskinetic effect on levodopa-induced dyskinesia. We determined the effects of nicotine on levodopa pharmacokinetics and gastric emptying in healthy subjects and on levodopa transport in Caco-2 monolayers in vitro.
Healthy subjects received transdermal nicotine patch application followed by oral levodopa/benserazide, 100/25 mg, in a fasting state and with enteral nutrition. Levodopa pharmacokinetics was determined, and gastric emptying was evaluated by carbon 13 ((13)C)-labeled acetic acid breath testing. In vitro studies using intestinal Caco-2 cell monolayers evaluated whether the intestinal transport of levodopa was affected by nicotine and its metabolite, cotinine.
Nicotine did not increase mean plasma concentration significantly during fasting or with enteral nutrition, although the extent of levodopa absorption was reduced by 34% to 60% in some individuals and the mean plasma concentration of levodopa was statistically decreased by nicotine in subjects who received enteral nutrition. However, gastric parameters were not significantly affected by nicotine. Nicotine and cotinine at 0.1 μmol/L significantly reduced levodopa uptake by Caco-2 cells (P < 0.01).
We found that nicotine reduced plasma levodopa concentration in some healthy subjects but with no alteration of gastric emptying rate. In vitro, nicotine inhibited levodopa transport by Caco-2 cell monolayers in an α-methyl amino isobutyric acid-independent, 2-amino-norbornanecarboxylic acid-dependent manner. These results suggest that nicotine may inhibit the transport of levodopa by the system L-amino acid transporter.
一些帕金森病患者在使用尼古丁贴片或口香糖治疗后症状有所改善。尼古丁对左旋多巴诱发的异动症的抗异动作用也已得到研究。我们测定了尼古丁对健康受试者左旋多巴药代动力学和胃排空的影响，以及其在体外对Caco-2单层细胞中左旋多巴转运的影响。
健康受试者在禁食状态下和接受肠内营养时，先使用经皮尼古丁贴片，随后口服100/25 mg左旋多巴/苄丝肼。测定左旋多巴药代动力学，并通过碳13（13C）标记的乙酸呼气试验评估胃排空情况。使用肠Caco-2细胞单层进行的体外研究评估了尼古丁及其代谢物可替宁是否会影响左旋多巴的肠道转运。
尽管在一些个体中左旋多巴的吸收程度降低了34%至60%，且在接受肠内营养的受试者中，尼古丁使左旋多巴的平均血浆浓度在统计学上有所降低，但尼古丁在禁食或肠内营养期间均未显著提高平均血浆浓度。然而，胃参数未受到尼古丁的显著影响。0.1 μmol/L的尼古丁和可替宁显著降低了Caco-2细胞对左旋多巴的摄取（P < 0.01）。
我们发现尼古丁降低了一些健康受试者的血浆左旋多巴浓度，但未改变胃排空率。在体外，尼古丁以不依赖α-甲基氨基异丁酸、依赖2-氨基降冰片烷羧酸的方式抑制Caco-2单层细胞对左旋多巴的转运。这些结果表明，尼古丁可能通过L-氨基酸转运系统抑制左旋多巴的转运。
