氟他胺大鼠在体肠吸收动力学研究

Intestinal Absorption Kinetics Studies of Flutamide in Rats

目的:研究氟他胺在大鼠小肠各段的吸收动力学特征,为其剂型设计提供依据。方法:采用在体试验法,分别用紫外可见分光光度法及高效液相色谱法(HPLC)测定酚红和氟他胺的浓度。结果:在体全小肠段吸收实验中,药液在体循环6 h后,43.58%的药物被肠道吸收;氟他胺在十二指肠、空肠、回肠、结肠的吸收百分率分别为(10.66±2.98)%.cm-1.h-1、(10.12±3.05)%.cm-1.h-1、(10.47±3.1)%.cm-1.h-1、(10.11±3.02)%.cm-1.h-1,四个肠段的肠壁通透系数分别为:(0.587±0.208)cm2.h-1、(0.571±0.193)cm2.h-1、(0.593±0.197)cm2.h-1、(0.539±0.192)cm2.h-1;药物浓度为15.48～68.48μg.mL-1时,小肠的吸收速率在(0.092±0.010)h-1～(0.090±0.012)h-1之间基本相似;供试药液中聚山梨酯-80的含量分别为1%、2%、5%时,肠的吸收速率分别为:(0.097±0.017)h-1、(0.078±0.012)h-1、(0.073±0.009)h-1。结论:氟他胺在大鼠肠道各部分均有吸收,且吸收呈一级动力学过程,吸收机制为被动扩散;实验范围内,药物浓度和聚山梨酯-80含量对药物的吸收速率无影响;大鼠各肠段的吸收速度无显著性差异,说明氟他胺在整个肠段均有较好的吸收。

Objective： To investigate the absorption of flutamide（FLU） in intestine of rats and provide biological pharmaceutical basis for dosage form design.Methods： The absorption kinetics was investigated in rats using an intestine perfusion method.UV-visible sepectrophotometer and HPLC were used to determine the concentrations of phenol red and flutamide,respectively.Results： About 43.58% of the drug was absorbed after a 6-h circulation.The absorption percentages of FLU in duodenum,jejunum,ileum and colon were（10.66±2.98）%·cm-1·h-1,（10.12±3.05）%·cm-1·h-1,（10.47±3.11）%·cm-1·h-1 and（10.11±3.02）%·cm-1·h-1,respectively,and their permeability coefficients（Ke） were（0.587±0.208）cm2·h-1,（0.571±0.193）cm2·h-1,（0.593±0.197）cm2·h-1 and（0.539±0.192）cm2·h-1,respectively.The apparent absorption constants（Ka） at different drug concentration levels（15.48~68.48 μg·mL-1） were（0.092±0.010） h-1^（0.090±0.012） h-1.The values of Ka were（0.097±0.017） h-1,（0.078±0.012） h-1 and（0.073±0.009） h-1 when the tween-80 concentrations in the solution were 1%,2% and 5%,respectively.Conclusion： Flutamide is absorbable in all segments of rat intestine in the pattern of first-order kinetics with a passive diffusion absorption mechanism;concentrations of drug and tween-80 in solution have no effect on the absorption kinetics;The variation of FLU Ka is inconspicuous at different segments of the intestine,indicating that FLU is suitable for oral sustained-released formulations.