马来酸曲美布汀大鼠肠吸收动力学研究

Kinetics of trimebutine maleate absorption in rat intestines

目的研究马来酸曲美布汀在大鼠不同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循环法研究马来酸曲美布汀的吸收部位和吸收动力学特征,利用紫外-可见分光光度法和反相-高效液相色谱法分别测定肠循环液中酚红和甲硝唑浓度。结果马来酸曲美布汀在十二指肠、空肠、回肠及结肠中的吸收速度常数分别为0.230±0.023、0.084±0.051、0.202±0.021、0.170±0.038(h-1),不同药物浓度(10、20、25μg/ml)在小肠的吸收速率常数分别为0.393±0.044、0.354±0.017、0.365±0.075(h-1),胆总管引流与不引流时药物在小肠的吸收速率常数分别为0.354±0.017、0.370±0.014(h-1)。结论马来酸曲美布汀在全肠段中均有吸收,吸收在10～25μg/ml浓度范围内符合一级动力学特征,吸收机制为被动扩散,胆汁排泄对药物吸收影响不大。

Objective To investigate the absorption kinetics of trimebutine maleate （TMB） at different intestinal segments in rats, and provide biological pharmaceutical basis for dosage design. Methods The absorption kinetics of TMB at different intestinal segments in rats was studied by in situ recirculation. UV and RP-HPLC were used to determine the concentrations of phenol red and TMB, respectively. Results The apparent absorption constants （ka） in duodenum, jejunum, ileum and colon were 0.230±0.023, 0.084±0,051, 0.202±0.021, 0.170±0.038（h^-1）, respectively. Intestinal ka of TMB at different concentrations （10, 20, 25 μg/ml） were 0.393±0.044, 0.354±0.017, 0.365±0.075（h^-1）, respectively, ka of TMB with or without bile duct-drainage were 0.354±0.017, 0.370±0.014（h^-1）, respectively. Conclusion TMB appeared absorbable in all segments of rat intestine. The intestinal absorption rate of TMB followed first-order kinetics and was consistent with passive transportation over the concentration range of 10-25 μg/ml. The intestinal absorption of TMB was not influenced by excretion of bile.