title: Pharmacokinetics, excretion, and distribution of combretastatin A4 phosphate in rats.
abstract: In order to characterize the pharmacokinetics, excretion, and distribution of combretastatin A4 phosphate (CA4P) and its active metabolite, combretastatin A4 (CA4), in rats, a reliable gradient HPLC-based method has been developed and validated. The pharmacokinetic profiles of CA4P and CA4 in rats after CA4P intravenous injection at doses of 0.7, 1 and 4 mg x kg(-1) were best described by a two-compartment model. The terminal half-lives of CA4P or CA4 were similar at different CA4P dose levels, 5-9 min for CA4P and 39-60 min for CA4, while t1/2alpha, and Vd of CA4P or CA4 were very different. CA4 was largely distributed to the heart, intestine, lung, spleen and liver during 15 to 40 min after intravenous injection of CA4P. CA4P was predominantly excreted into urine (10.72%) and feces (9.703%) and to a lesser extent into bile (0.897%), whereas a greater portion of CA4 were excreted into feces (6.235%) and to a lesser extent into urine (0.782%) and bile (0.496%) during 0-28 h after intravenous injection of 1 mg x kg(-1) to rats. This is the first study to characterize the distribution of the active CA4P metabolite, CA4, in rat.
authors: West China School of Pharmacy, Sichuan University, Chengdu, China.
authors: Xiao-Ping
authors: XP
authors: Xu
authors: Xiao-Dong
authors: XD
authors: Wu
authors: Gui-Lun
authors: GL
authors: Liang
authors: Wen-Sheng
authors: WS
authors: Huang
authors: Li
authors: L
authors: Wang
authors: Hai-Ying
authors: HY
authors: Jing
authors: Shi-Long
authors: SL
authors: Zhong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D057230:Limit of Detection; D010710:Phosphates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D012044:Regression Analysis; D015203:Reproducibility of Results; D013267:Stilbenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D010710:Phosphates; D013267:Stilbenes; C058728:fosbretabulin