Pharmacokinetics of recombinant human endostatin in rats.
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 (t1/2beta) 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 t1/2beta 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.
Yang
Xiao-Xia
XX
Department of Pharmacy, Faculty of Science, National University of Singapore, Science Drive 4, Singapore 117543, Singapore.
Hu
Zen-Ping
ZP
Chan
Eli
E
Duan
Wei
W
Zhou
Shufeng
S
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000378:metabolism; D043169:Endostatins / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D011994:Recombinant Proteins