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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 g.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 g.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 g.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 g.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 intestinal absorption of asiatic acid (AA). Methods The rats were in vivo uni-directional perfusion as the absorption model. The drug concentration in intestinal perfusate was determined by HPLC. The absorption kinetics of AA was investigated. The absorption coefficient (Peff) The rate constant (Ka) and the drug absorbed dose fraction (fa) were used to evaluate the absorption properties of the drug. Results AA was linear within 1.0 ~ 18.0 g.mL 1. Perfusion experiments showed that the absorption curve of AA approximated the linear state, and the cumulative absorption of drug increased with the increase of drug concentration in perfusate. The Peff of high concentration perfusate (30 g · mL 1) was (0.48 ± 0.04) × 10 4.cm 1.s 1, Ka was (0.34 ± 0.06) × 10 3.s 1 and fa was (52.50 ± 3.08) %, Peff of low concentration perfusate (9 g · mL 1) was (0.55 ± 0.14) × 10 4.cm 1.s 1, Ka was (0.34 ± 0.05) × 10 3.s 1 and fa was (56.53 ± (P <0.05). When the concentration of perfusate was 30 g.mL 1, the fa of duodenum, jejunum, ileum and colon were (59.59 ± 13.08%, 63.34 ± 11.48%, 66.95 ± 8.01%, 39.43 ± 14.96%, respectively. Conclusion AA belongs to the moderate degree of absorption of drugs, which are absorbed in the whole intestinal segment, and the ileum is the best. The absorption mechanism should be passive diffusion.