积雪草酸的大鼠在体肠吸收动力学研究

Study on the Intestinal Absorption Kinetics of Asiatic Acid in Rats

目的 考察积雪草酸（asiatic acid，AA）的肠吸收特性。方法 以大鼠在体单向灌流为吸收模型，采用所建立的高效液相色谱法检测肠灌流液中的药物浓度，考察AA的吸收动力学，并通过肠腔有效吸收系数（Peff）、吸收速率常数（Ka）和药物吸收剂量分数（fa）评价药物的吸收特性。结果 AA在1.0~18.0 mg·mL^-1内呈线性。灌流试验表明，AA的吸收曲线近似于线性状态，药物累积吸收量随着灌流液药物浓度的增加而提高。高浓度灌流液（30 mg·mL^-1）的Peff为（0.48±0.04）×10-4·cm-1·s-1，Ka为（0.34±0.06）×10-3·s-1，fa为（52.50±3.08）%，低浓度灌流液（9 mg·mL^-1）的Peff为（0.55±0.14）×10-4·cm-1·s-1，Ka为（0.34±0.05）×10-3·s-1，fa为（56.53±10.25）%，两者Peff、Ka和fa无显著性差异（P〉0.05）；当灌流液浓度为30 mg·mL^-1时，十二指肠、空肠、回肠、结肠的fa分别为（59.59±13.08）%、（63.34±11.48）%、（66.95±8.01）%、（39.43±14.96）%。结论 AA属于中等程度吸收药物，在整条肠段均有吸收，以回肠最好；其吸收机制应属被动扩散。

OBJECTIVE To investigate the absorption characteristics of asiatic acid（AA） in rats. METHODS In situ single pass perfusion mode was used and the HPLC method was established to explore the absorption kinetics of AA, the drug absorption was evaluated by effective permeability （Peff）, absorption rate constant （Ka） and fraction absorbed （fa）. RESULTS The calibration curve was found to be linear over the concentration range of 1.0~18.0 mg·mL-1. With the increase of AA concentration, the accumulative absorption of AA was increased, and its absorption curve was shown to be linear. Peff, Ka and fa of AA at concentration of 30 mg·mL^-1 was （0.48±0.04）×10-4·cm-1·s-1, （0.34±0.06）×10-3·s-1, （52.50±3.08）%, respectively. It was （0.55±0.14）×10-4·cm-1·s-1, （0.34±0.05）× 10-3·s-1, （56.5±10.25）% at concentration of 9 mg·mL-1, respectively. There was no significant difference of absorption parameters at concentration of 30 and 9 mg·mL-1（P〉0.05）. The fa of AA at concentration of 30 mg·mL^-1 at duodenum, jejunum, ileum and colon was （59.59±13.08）%, （63.34±11.48）%, （66.95±8.01）%, （39.43±14.96）%, respectively. CONCLUSION AA can be classified into intermediate penetrating drug. It can be absorbed at all intestinal segments, and ileum was the best absorption segment. Its absorption is mainly via passive transport mechanism in intestine.