Department of Clinic Pharmacy, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, People's Republic of China.
Department of Clinic Pharmacy, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, People's Republic of China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 15;961:20-8. doi: 10.1016/j.jchromb.2014.04.038. Epub 2014 May 5.
Nuciferine is an important drug candidate for the treatment of obesity-related diseases. However, few investigations have been conducted about the pharmacokinetics and tissue distribution of nuciferine to better understand its behavior and action mechanism in vivo. Thus, a sensitive and reliable liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was established and validated for the quantification of nuciferine in rat plasma and tissue samples. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of nuciferine in rats. One-compartmental pharmacokinetic parameters indicated that nuciferine had rapid distribution, extensive tissue uptake, and poor absorption into systemic circulation. The values of absolute bioavailability were (3.8±1.4)%, (4.2±1.3)% and (3.9±1.0)% after oral administration of 2.0, 5.0 and 10.0mg/kg nuciferine and intravenous administration of 0.2mg/kg nuciferine in rats. The results of the tissue distribution study suggested that nuciferine was distributed into the brain, liver and adipose tissue after intravenous administration. In conclusion, the present study may provide a material basis for study of the pharmacological action of nuciferine in the treatment of obesity, and meaningful insights into further study on dosage modification.
荷叶碱是治疗肥胖相关疾病的重要候选药物。然而,关于荷叶碱的药代动力学和组织分布的研究较少,难以深入了解其在体内的行为和作用机制。因此,建立并验证了一种灵敏、可靠的液相色谱-串联质谱(HPLC-MS/MS)法,用于大鼠血浆和组织样品中荷叶碱的定量分析。该方法成功应用于荷叶碱在大鼠体内的药代动力学和组织分布研究。单室模型药代动力学参数表明,荷叶碱分布迅速,广泛摄取组织,吸收进入体循环较差。大鼠灌胃给予 2.0、5.0 和 10.0mg/kg 荷叶碱及静脉给予 0.2mg/kg 荷叶碱后,其绝对生物利用度分别为(3.8±1.4)%、(4.2±1.3)%和(3.9±1.0)%。组织分布研究结果表明,静脉给予荷叶碱后可分布于脑、肝和脂肪组织。总之,本研究可为荷叶碱治疗肥胖的药理作用研究提供物质基础,并为进一步研究剂量调整提供有意义的见解。