洛伐他汀在巴马香猪体内的分布和排泄

目的研究洛伐他汀在巴马香猪体内的分布和排泄特点。方法以抗动脉粥样硬化药物洛伐他汀为模型药,选择健康6月龄雄性巴马香猪为实验对象,经灌胃途径给药(45 mg/kg或2.4 mg/kg),采用RP-HPLC方法测定各组织及体液中的药物浓度,并对其分布和排泄过程进行研究。血浆蛋白结合率通过透析法测定。结果给药后,洛伐他汀快速分布到贲门、胃、小肠、肝、大肠、胰、前列腺、肺、肾、心、肌肉、睾丸、肾上腺、膀胱、脑和脾。以胃、肠、肝组织中药物浓度较高。单次给药4h后,贲门、胃、小肠、肝、心、肾上腺、膀胱药物浓度同给药后1h相比略有下降,其余组织均高于1 h。血浆蛋白结合率为95%以上,同正常人血浆非常一致。96 h尿中累积排泄量为给药量的7.4%,原形药经胆汁及粪排泄量达到80%以上。结论洛伐他汀在巴马香猪体内同人的分布排泄和血浆蛋白结合率相似,均在组织中广泛分布,血浆结合率达到95%以上,主要经胆汁和粪排泄。

Distribution and Excretion of Lovastatin in Bama Miniature Pigs

Objective To study the distribution and excretion of lovastatin in Bama minipigs.Methods The concentration of lovastatin in tissues and body-fluid in 6-month old male Bama minipigs after oral administration were detected by RP-HPLC.The serum protein binding rate in pigs was determined by dialysis method.Results Lovastatin was showed to be widely distributed in many organs after i.g.administration of 45 mg/kg.The higher level of lovastatin was found in the stomach,intestine and liver.The concentrations in stomach,small intestine,liver,heart,adrenal and bladder at 1 h were higher than those at 4 h.7.4% of the given dose was excreted in unchanged form in urine within 96 h.More than 80% was excreted in bile and feces within 96 h.The plasma protein binding ratio was higher than 95%.Conclusion It could be concluded that distribution,excretion and the plasma protein binding ratio of lovastatin in the Bama minipigs are similar to those in humans.