摘要
目的研究比较多西他赛（docetaxel,DTX）亚微乳注射剂及普通注射剂在大鼠体内的组织分布及原型药物的排泄情况。方法以DTX注射剂（商品名：泰索帝）为参比,48只SD大鼠随机分成2组,分别经尾静脉注射DTX亚微乳注射剂（75 mg.m-2）和DTX注射剂（75 mg.m-2）,在给药后5、30、60、300 min各处死6只大鼠,于相应部位取各组织适量。另取大鼠10只,随机分为2组,分别静脉注射亚微乳注射剂或普通注射剂（75 mg.m-2）,收集给药前及给药后0~4、4~10、10~18、18~24、24~36 h的尿液、粪便。组织及排泄物中的DTX浓度以HPLC-UV法测定。结果 DTX亚微乳注射剂及普通注射剂在体内分布广泛而迅速。DTX亚微乳在心和肺中的浓度显著低于注射剂（P〈0.05）,但在脾脏中的浓度高于注射剂（P〈0.05）。肾脏中的分布在早期较注射剂明显增加,后期较注射剂明显降低（P〈0.05）,其他组织器官的分布无显著性差异（P〉0.05）。两者经粪便和尿液排泄的原型药物无显著性差异（P〉0.05）,36 h尿排累积百分率均〈2%,粪排累积百分率均〈6%。结论与普通注射剂相比,亚微乳不影响DTX在大鼠体内的原型药物排泄。在安全性及药效学评价中,应特别关注剂型改变后心、肺、肾及脾脏的毒性及药效变化。
Objective To investigate tissue distribution and excretion of docetaxel submicron emulsion in rats.Methods A high performance liquid chromatography（HPLC） with UV detection was developed to study the concentration of docetaxel in the biological samples.Taking paclitaxel as an internal standard,48 SD rats were randomly divided into 2 groups：test preparation and reference preparation,and each group was intravenously administered 75 mg·m-2 DTX.The rats were executed at 5,30,60 and 300 min,and tissues were taken in the same location to determine the content.Results The docetaxel submicron emulsion was widely distributed in the tissues of the body.The docetaxel concentration of the test group in the heart and lung was lower than that of the reference group（P〈0.05）,but higher than the reference group in the spleen（P〈0.05）.In the kidney,the docetaxel concentration of the test group increased quickly before 30 min and was higher than the reference group（P〈0.05）,and after that the concentration decreased even lower than the reference injection（P〈0.05）.The docetaxel concentrations of the 2 groups in other tissues and organs had no significant difference（P〉0.05）.The excretion of the parent drug in the urine and excrement amounted to 2% and 6% of the dose,respectively.Conclusion Submicron emulsion has no significant effect on docetaxel distribution and the preparation is delivered effectively.In safety and pharmacodynamic evaluation,we should pay more attention to the alteration of toxicity and therapeutic effect after changing dosage forms.
出处
《中南药学》
CAS
2011年第6期409-413,共5页
Central South Pharmacy
基金
国家科技型中小企业创新基金资助项目(No.:07C26214601864)
关键词
多西他赛
亚微乳
组织分布
排泄
docetaxel
submicron emulsion
distributionl excretion
