依托度酸大鼠在体肠吸收动力学

目的考察依托度酸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依托度酸在大鼠各肠段的吸收动力学特征;采用高效液相色谱法(HPLC)测定灌流液中依托度酸的含量;从药物质量浓度、吸收部位、灌流速度、pH值4个方面对依托度酸的各肠段吸收特性进行考察;利用重量法计算动力学参数。结果灌流速度和一定范围内的pH值(5.4～7.4)对药物吸收速率常数(ka)和表观吸收系数(Papp)影响显著;一定范围内的药物浓度对ka和Papp无显著影响;十二指肠、空肠、回肠和结肠的ka值分别为(0.082 7±0.003 8)、(0.077 5±0.004 5)、(0.073 3±0.006 4)、(0.064±0.009 3)min-1。结论依托度酸在大鼠肠道的吸收呈现一级动力学特征,且吸收机制为被动扩散。依托度酸在整个肠道均有吸收。

Intestinal absorption kinetics of etodolac in rats

Objective To investigate the in situ intestinal absorption kinetics of etodolac in rats. Methods In situ single-pass perfusion method was used to investigate the absorption of etodolac in different segments of rats; and the concentrations of etodolac in the perfusion were measured by HPLC. The absorption kinetics of etodolac at different drug concentration, segments of intestine, pH value and perfusion flow rate were studied; and the gravimetric method was utilized for the calculation of absorption kinetics parameters. Results Perfusion flow rate and pH value could significantly affect the drug absorption constant (k_a) and apparent absorption coefficient (P_app) .Concentration of etodolac had little effect on k_a and P_app. The constants of absorption rate at duodenum, jejunum, ileum, and colon were (0.0827±0.0038), (0.0775±0.0045), (0.0733±0.0064), (0.064±0.0093) min^-1, respectively. Conclusions The absorption of etodolac is a first-order process with the passive diffusion mechanism. Etodolac can be absorbed at all segments of the intestine in rats.