摘要
研究了青藤碱在大鼠的药动学节律。用Ｗｉｓｔａｒ大鼠，在自然昼夜节律条件下，自由摄食和饮水。选择卯时（早７时）和酉时（晚７时）给予相同剂量的青藤碱，在给药后不同的时间点采取血桨和脑组织，用ＨＰＬＣ法测定血浆和脑中的青藤碱浓度，结果表明，卯时给药，血浆中和脑中的青藤碱浓度明显高于酉时（Ｐ＜０．０５）。无论是卯时还是酉时给药，青藤碱血中的药时曲线均可用开放型二房室模型描述，但动力学参数存在着较大的差异，卯时给药Ｃｍａｘ４４．５ｍｇ／Ｌ，Ｋ１００．４４ｈ－１，ＡＵＣ９８．７５ｍｇ·ｈ／Ｌ，Ｔ１／２α０．１３ｈ，Ｔ１／２β３．９９ｈ和Ｖｄ０．４５Ｌ／ｋｇ；酉时给药，Ｃｍａｘ１６．７ｍｇ／Ｌ，Ｋ１００．３０ｈ－１，ＡＵＣ５５．０２ｍｇ·ｈ／Ｌ，Ｔ１／２α０．２４ｈ，Ｔ１／２β３．３１ｈ和Ｖｄ１．２０Ｌ／ｋｇ。本研究提示青藤碱的药代动力学受生物节律依赖性的影响。
The circadian pharmacokinetics of sinomenine in rodent was studied. Under naturalcircadian rhythms , Wistar rats were allowed to take food and drink water freely. The same dose ofsinomenine was given at 7:00 AM and 7:00 PM. Their plasma and brain tissues were sampled beforemedication and at different intervals after medication. The concentrations of sinomenine in plasma andbrain were determined by HPLC with UV detector. It was shown that the concentrations in plasma andbrain after the morning dose were much higher than those after the evening dose (P <0.05) . Thepharmacokinetics analysis of two-compartment open model showed that the values of pharmacokinetic parameters of two groups appeared quite different, i.e., Cmax 44.5mg/L, K10 0.45h-1 , AUC 98.75mg · h/L,T1/2α 0.13h, T1/2β 3.89h and Vd 0.45L/kg, in day group, and Cmax 16.7mg/L, K10 0.30h-1, AUC 55.02mg·h/L, T1/2α 0.24h, T1/2β 3.31h and Vd 1.20L/kg in night group. This study showed that the pharmacokineticsof sinomenine in rodents is influenced by the circadian rhythmic dependency.
出处
《中药新药与临床药理》
CAS
CSCD
1995年第1期23-26,共4页
Traditional Chinese Drug Research and Clinical Pharmacology
