普伐他汀在大鼠小肠中的吸收和肝脏中的分布

Study on Intestinal Absorption and Liver Distribution of Pravastatin in Rats

目的研究普伐他汀在大鼠小肠吸收及肝脏分布特征。方法30只大鼠随机分为3组,分别在大鼠小肠不同区段注入普伐他汀钠溶液1 mg,1 h后处死大鼠,采集肠内容物及肝组织,HPLC和HPLC-MS测定其中普伐他汀及其主要代谢物3′α-异普伐他汀的浓度。结果普伐他汀的吸收百分率、肝组织中普伐他汀和3′α-异普伐他汀的浓度均按十二指肠、空肠、回肠顺序依次下降。各肠段普伐他汀的吸收百分率差别均有统计学意义(P<0.05);十二指肠给药和空肠给药后、空肠给药和回肠给药后肝组织中普伐他汀的浓度差别均无统计学意义(P>0.05),十二指肠给药和回肠给药后差别有统计学意义(P<0.05);不同肠段给药后肝组织中3′α-异普伐他汀的浓度差别无统计学意义(P>0.05)。结论普伐他汀主要在小肠中上部吸收,最佳吸收部位在十二指肠;普伐他汀肝脏分布量与小肠吸收量成正相关。提示应改良现有制剂,增加其在小肠中上部的吸收。

OBJECTIVE To study the intestinal absorption and liver distribution characters of pravastatin in rats.METHODS Thirty SD rats were randomly assigned to 3 groups. Rats received 1 mg pravastatin sodium by being injected respectively to different parts of the intestine. The rats were killed at 1 h after administration. Pravastatin concentrations in the intestine and liver samples were, determined by a HPLC or HPLC-MS method. RESULTS The absorption percentage of pravastatin, the concentrations of pravastatin and 3′α-isopravastatin in the liver were decreased gradually after intraduodenal, intrajejunal and intraileal administration. ANOVA showed statistically significant difference in the absorption percentage of pravastatin in different parts of the intestine（ P 〈 0.05）. There was no statistically significant difference in the pravastatin concentrations in the liver after intraduodenal and intrajejunal administration, or after intrajejunal and intralleal administration （ P 〉 0.05 ）. There was statistically significant difference after intraduodenal and intraileal administration （ P 〈 0.05）. There was no statistically significant difference in the concentrations of 3′α-isopravastatin in the liver after administration at the different parts of the intestine （ P 〉 0.05）. CONCLUSION Pravastatin was mainly absorbed from the upper and middle parts of the small intestine, while the duodenum was the best site for the absorption. The pravastatin concentration in the liver correlates positively with the absorption amount. The results indicate that the present preparation of pravastatin should be modified in order to increase the absorption of pravastatin in the upper and middle parts of the small intestine.