Hao Kun, Liu Xiao-Quan, Wang Guang-Ji, Zhao Xiao-Ping
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People's Republic of China.
Eur J Drug Metab Pharmacokinet. 2007 Apr-Jun;32(2):63-8. doi: 10.1007/BF03190993.
The plasma pharmacokinetics, excretion, and tissue distribution of gambogic acid (GA), a novel anti-tumor drug, were investigated after intravenous (i.v.) bolus administration in rats. Plasma profiles were obtained after i.v. administration of GA at the doses of 1, 2 and 4 mg/kg. The elimination half-life (tl/2) values for GA were estimated to be 14.9, 15.7 and 16.1 min, while the mean area under concentration-time curve (AUC(t)) values were 54.2, 96.1 and 182.4 microg min/ml, respectively. GA was mainly excreted into the bile (36.5% over 16 h). The cumulative sum of fecal excretion within 48 h was 1.26% of the i.v. administered dose. No GA was detected in the urine after i.v. administration. GA had a limited tissue distribution, with the highest concentrations being found in the liver. GA reached its maximal concentration in all tissues at 5 min post-dose. In conclusion, the present observations indicated that GA was rapidly eliminated from the blood and transferred to the tissues. Moreover, the majority of GA appeared to be excreted into the bile within 16 h of i.v. administration.
在大鼠静脉推注给药后，对新型抗肿瘤药物藤黄酸（GA）的血浆药代动力学、排泄及组织分布进行了研究。以1、2和4mg/kg的剂量静脉注射GA后获得血浆浓度曲线。GA的消除半衰期（t1/2）值估计分别为14.9、15.7和16.1分钟，而浓度-时间曲线下平均面积（AUC(t)）值分别为54.2、96.1和182.4μg·min/ml。GA主要经胆汁排泄（16小时内排泄36.5%）。48小时内粪便排泄累积量为静脉给药剂量的1.26%。静脉给药后尿液中未检测到GA。GA的组织分布有限，肝脏中浓度最高。给药后5分钟时GA在所有组织中均达到最高浓度。总之，目前的观察结果表明，GA在血液中迅速消除并转移至组织中。此外，大部分GA在静脉给药后16小时内似乎经胆汁排泄。
