Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.
Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.
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DOI：
10.1016/j.pharep.2014.12.004
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Bartlett MG
中科院分区：
文献类型：
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作者：
Li P;Beck WD;Callahan PM;Terry AV Jr;Bartlett MG
可替宁（COT）是尼古丁（NIC）的主要代谢产物之一，因其对阿尔茨海默病（AD）和其他类型认知障碍的促认知作用和潜在治疗活性而受到关注。为了促进COT的药理学和毒理学研究，以促进其认知活动，我们进行了大鼠中的COT的药代动力学（PK）研究，提供了重要的口服和静脉注射（IV）PK信息。在本研究中，大鼠经口和IV给予COT（剂量为3 mg/kg）后48小时内采集血浆样本。使用灵敏的液相色谱串联质谱（LC-MS/MS）生物分析方法制备和分析血浆样本，提供口服和IV给药后COT和代谢产物的浓度曲线。将口服组和IV组的数据分别拟合为一室模型和二室模型，为COT提供了重要的PK信息，包括PK特征、半衰期、清除率和生物利用度。结果表明，COT在大鼠体内吸收快，消除慢，生物利用度高。关于大鼠PK特性的几个重要事实表明，COT可能是一种潜在的促认知剂。本研究所揭示的COT在大鼠体内的药代动力学信息，对于进一步研究COT或潜在的COT类似物作为改善认知功能的药物具有重要意义。
Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's Disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (IV) PK information. In this study, plasma samples were obtained up to 48 hours after COT was dosed to rats orally and IV at a dose of 3 mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and IV administrations. The data were fitted into a one-compartment model and a two-compartment model for the oral and IV groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogues as agents for improving cognition.