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Title: Pharmacokinetics of recombinant human endostatin in rats
Authors: Yang, X.-X.
Hu, Z.-P.
Chan, E. 
Duan, W.
Zhou, S. 
Keywords: Allometric scaling
Issue Date: Aug-2006
Source: Yang, X.-X., Hu, Z.-P., Chan, E., Duan, W., Zhou, S. (2006-08). Pharmacokinetics of recombinant human endostatin in rats. Current Drug Metabolism 7 (6) : 565-576. ScholarBank@NUS Repository.
Abstract: The pharmacokinetics of recombinant human endostatin (rh-Endo) has not been established in the rat, although this species of animal is commonly used in the pharmacological studies of rh-Endo. This study aimed to investigate the pharmacokinetics, tissue distribution, and excretion of rh-Endo in rats. 125I-radiolabeled rh-Endo was administered to healthy rats by intravenous (i.v) bolus injection at 1.5, 4.5 and 13.5 mg/kg. The maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of rh-Endo increased proportionally with the increase of the dosage. There were no significant differences in total body clearance (CL) and elimination half-life (t1/2β) of rh-Endo among the three dosages used. A 93.5% and 2.2% of the radioactivity was recovered in the urine and feces, respectively, in bile-duct intact rats; whereas only 0.1% of the total radioactivity was excreted into the bile in bile-duct cannulated rats. rh-Endo was rapidly and widely distributed in the liver, kidneys, spleen and lungs. Furthermore, a significant allometric relationship between CL, but not volume of distribution (Vd) and t1/2β of rh-Endo, and the body weight was observed across mouse, rat and monkey, with the predicted values in humans significantly lower than those observed in cancer patients. rh-Endo exhibited a linear pharmacokinetics in rats and it is mainly excreted through the urine. © 2006 Bentham Science Publishers Ltd.
Source Title: Current Drug Metabolism
ISSN: 13892002
DOI: 10.2174/138920006778017803
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