阿替洛尔大鼠在体胃肠道吸收动力学研究

Gastrointestinal Absorption Kinetics Studies of Atenolol in Rats

目的:研究阿替洛尔在大鼠胃、肠及各肠段的吸收动力学特征,为其剂型设计提供生物药剂学依据。方法:采用大鼠在体肠灌流实验,利用紫外-可见分光光度法和HPLC法分别测定酚红和阿替洛尔的含量。结果:药物在胃和小肠中2 h的吸收百分率分别为8.63%±1.04%、8.91%±2.73%;阿替洛尔在十二指肠、空肠、回肠、结肠的吸收速率常数各为(0.0706±0.0161)h-1、(0.0360±0.0111)h-1、(0.0465±0.0126)h-1、(0.0479±0.0083)h-1;药物质量浓度为20、50、100μg.mL-1时,在肠的吸收速率常数分别为(0.0568±0.0308)h-1、(0.0360±0.0111)h-1、(0.0531±0.0095)h-1;当pH值为5.0、6.5、7.4时,肠的吸收速率常数分别为(0.0528±0.0051)h-1、(0.0603±0.0322)h-1、(0.0465±0.0126)h-1。结论:阿替洛尔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;药物在大鼠肠内的吸收不受药物浓度和pH的影响;药物的吸收按十二指肠、结肠、回肠、空场的顺序依次下降。

Objective： To investigate the absorption kinetics of atenolol（AT） in the gastro-intestine of rats,to provide the biological pharmaceutical basis for dosage design.Methods： The absorption kinetics was investigated in rats using an intestine perfusion method.UV and RP-HPLC were used to determine the concentrations of phenol red and atenolol,respectively.Results： The absorption percentages of atenolol in stomach,small intestine were 8.63%±1.04% and 8.91%±2.73%,respectively.The apparent absorption constants（Ka） in duodenum,jejunum,ileum and colon were（0.0706±0.0161） h-1,（0.0360±0.0111） h-1,（0.0465±0.0126） h-1,（0.0479±0.0083） h-1,respectively.Intestinal Ka of AT at different concentrations（20,50 and 100 μg·mL-1） were（0.0568±0.0308） h-1,（0.0360±0.0111） h-1,（0.0531±0.0095） h-1,respectively.Ka at pH of 5.0,6.5 and 7.4 for the whole intestine were（0.0528±0.0051） h-1,（0.0603±0.0322） h-1,（0.0465±0.0126） h-1,respectively.Conclusion： Atenolol is absorbable in all segments of rat gastro-intestine in the pattern of first-order kinetics with the passive diffusion absorption mechanism;concentration and pH of the drug solution have no effect on the absorption kinetics;the absorption at duodenum,jejunum,ileum and colon align in a decreasing order.