双氯芬酸钠大鼠在体肠吸收的研究

Intestinal Absorption in Situ of Diclofenac Sodium in Rat

目的评价双氯芬酸钠在大鼠不同肠段的吸收特征,为其剂型设计提供依据。方法采用大鼠单向灌流模型、高效液相法测定在体灌流液中双氯芬酸钠的浓度,计算吸收性能参数。结果双氯芬酸钠在十二指肠、空肠、回肠及结肠中的吸收速率常数分别为(5.28±0.68)、(6.42±0.95)、(8.47±0.69)、(5.89±0.51)(Ka,×10^-2/min);不同灌流药物浓度(5、10、20μg/mL)在小肠的表观吸收速率常数分别为(4.56±0.18)、(4.32±0.15)、(4.76±0.21)(Ka,×10^-2/min);不同体积流量(0.2、0.4、0.8mL/min)下,双氯芬酸钠在小肠的吸收速率常数分别为(4.32±0.15)、(5.88±0.14)、(6.92±0.18)(Ka,×10^-2/min)。结论双氯芬酸钠的肠吸收在5~20g/mL浓度范围内遵循一级动力学方程,主要为被动扩散吸收,在全肠道吸收均较好,适于制备缓控释制剂、肠溶制剂等。

Objective The aim of the study is To investigate the absorption characters of diclofenac sodium at different intestinal segments in rats for providing theoretical basis for dosage design.Methods The single-pass perfusion model in situ was established in rats,the concentration of diclofenac sodium in intestinal perfusion was determined by HPLC.Results The apparent absorption constants Ka in duodenum,jejunum,ileum and colon were(5.28±0.68),(6.42±0.95),(8.47±0.69),(5.89±0.51)(K a,×10^-2/min)respectively.Intestinal Ka of diclofenac sodium at different concentrations(5,10,20 g/mL)were(4.56±0.18),(4.32±0.15),(4.76±0.21)(K a,×10^-2/min)respectively.Intestinal Ka of diclofenac sodium at different volum eticflowrate(0.2,0.4,0.8 mL/min)were(4.32±0.15),(5.88±0.14),(6.92±0.18)(K a,×10^-2/min)respectively.Conclusion Diclofenac sodium appeared absorbable in all segments of rat intestine.The intestinal absorption rate of diclofenac sodium followed first-order kinetics and was consistent with passive transportation over the concentration range of 5~20 g/mL.These findings indicated that diclofenac sodium can be prepared as sustained release preparations or enteric-coated preparations.