【摘要】 目的:考察帕利哌酮在大鼠各肠段的吸收动力学特征。方法:运用大鼠在体单向灌流技术考察帕利哌酮在大鼠各肠段的吸收动力学特征;采用高效液相色谱法测定灌流液中帕利哌酮的含量;从药物质量浓度、吸收部位、灌流速度、介质pH值4个方面对帕利哌酮的各肠段吸收特性进行考察;利用重量法计算动力学参数。结果:药物的吸收在质量浓度较高时(10.0～20.0μg.mL-1)具有自身抑制现象。灌流速度和介质pH值在考察范围内对药物肠吸收影响显著。考察范围内的药物吸收部位对吸收速率无显著影响。十二指肠、空肠、回肠和结肠的Ka值分别为(6.58±2.35),(7.03±3.33),(7.13±2.77),(3.77±3.42)h-1。结论:帕利哌酮在整个肠道均有吸收,初步推断帕利哌酮在大鼠肠道的吸收机制为主动转运。更多还原

【Abstract】 Objective:To investigate the in situ intestinal absorption kinetics of paliperidone in rats.Methods:In-situ single-pass perfusion method was used to investigate the absorption of paliperidone in different segments of rats;and the concentrations of paliperidone in the perfusate were measured by HPLC.The absorption kinetics of paliperidone at different drug concentrations in different segments of intestine with perfusate at different pH values at different perfusion flow rates were studied;and gravimetric method was utilized for the calculation of absorption kinetics parameters.Results:Perfusion flow rate,pH value of perfusate and high drug concentration could significantly affect the drug absorption.The site of intestine segments had little effect on absorption.The constants of absorption rate at duodenum,jejunum,ileum,and colon were(6.58±2.35),(7.03±3.33),(7.13±2.77),and(3.77±3.42) h-1,respectively.Conclusion:Paliperidone can be absorbed at all segments of the intestine in rats.It is preliminarily inferred that the absorption mechanism of paliperidone is active absorption.更多还原