中国药理学与毒理学杂志2011，Vol.25Issue(2)：206-210,5.DOI:10.3867/j.issn.1000-3002.2011.02.015
抗肿瘤化合物MC002的活性代谢产物雷公藤内酯醇在大鼠体内药代动力学与组织分布
Pharmacokinetics and tissue distribution of triptolide, an active metabolite of anticancer prodrug MC002,in rats
摘要
Abstract
OBJECTIVE To investigate pharmacokinetics and tissue distribution properties of triptolide (TP), an active metabolite of a new anticancer prodrug MC002, in rats. METHODS SD rats were iv given MC002 0.25, 0.75 and 2.25 mg· kg-1, and blood samples were collected at 0, 2, 5, 8, 12, 16, 20, 30, 45, 60 and 90 min before and after administration of MC002. Tissues samples were collected at 5, 15, 30 and 90 min after SD rats were iv given MC002 0.75 mg·kg-1.Concentrations of TP in biological samples were determined by high performance liquid chromatorgraphy-mass spectrometry (HPLC-MS/MS). Pharmacokinetic parameters were calculated by DAS2.0 software. RESULTS After male SD rats were iv given MC002 0.25, 0.75 and 2.25 mg·kg-1,MC002 was quickly metabolized to TP, an active metabolite of MC002. AUC of TP in MC002 0.25,0.75 and 2.25 mg·kg-1 groups was 1827 ± 151,5604 ± 1141, and ( 16 833 ±3654) μg·min· L-1,respectively, cmax was 105±2,257 ±74 and (747 ± 154)μg· L-1, respectively, in a linear proportion to MC002 dose, and t1/2 was 31.7 ±7.3,23.8 ±3.4 and ( 19.2 ±2.5 ) min, respectively. After the administration of MC002 0.75 mg· kg-1, TP reached the peak concentration in all measured tissues at 5 min, but decreased significantly after 30 min. CONCLUSION Prodrug MC002 is quickly transformed into TP after rats are iv given MC002. TP conforms to linear pharmacokinetics within the range of 0.25 -2.25 mg· kg-1. TP is widely distributed but quickly eliminated in rats.关键词
MC002/雷公藤内酯/药代动力学/组织分布/抗肿瘤药分类
医药卫生引用本文复制引用
刘萍霞,刘频健,庄笑梅,王娟,张玉杰,张振清,阮金秀..抗肿瘤化合物MC002的活性代谢产物雷公藤内酯醇在大鼠体内药代动力学与组织分布[J].中国药理学与毒理学杂志,2011,25(2):206-210,5.基金项目
国家重大新药创制"科技重大专项新药研究开发技术单元平台"(2009ZX09304-004) （2009ZX09304-004）
北京市科委重大创新药物研制资助项目(D07080201330721) （D07080201330721）
