@article{APS3536,
author = {Hai-feng SONG and Xiu-wen LIU and Hai-ning ZHANG and Bao-zhen ZHU and Shou-jun YUAN and Shang-yi LIU and Zhong-ming TANG},
title = {Pharmacokinetics of His-tag recombinant human endostatin in Rhesus monkeys 1 },
journal = {Acta Pharmacologica Sinica},
volume = {26},
number = {1},
year = {2016},
keywords = {},
abstract = {Aim: To study the pharmacokinetics and accumulation of an Escherichia coliexpressed
His-tag fused recombinant human endostatin (rh-endostatin) in Rhesus
monkeys.
Methods: Rh-endostatin was iv or sc injected in Rhesus monkeys, and
the rh-endostatin concentration in serum samples was determined by an enzyme
immunoassay (EIA) method. The serum drug concentration-time data were analyzed
by compartmental analysis using the practical pharmacokinetic program 3p97.
Results: Following iv administration at a dose rate of 1.5, 4.5, and 13.5 mg/kg in
rhesus monkeys, the concentration-time curves of rh-endostatin were best fitted
to a three-compartment open model. AUC(0-∞) linearly increased with dose, while
Cls exhibited no significant difference among different dose groups. The terminal
half-lives (λ3) were 8±8, 3.1±1.4, and 20±14 h, respectively. After sc administration
at a dose rate of 1.5 mg/kg, the concentration-time curve was best fitted to a
two-compartment open model, with a terminal half-life (T1/2β) of 8±3 h.
Bioavailability following sc injection was approximately 70%±3%. After consecutive
iv injection of rh-endostatin at a dose rate of 1.5 mg•kg-1•d-1 for 7 d, the
AUC(0-24 h) substantially increased from 22±13 mg•h•L-1 (d 1) to 50±29 mg•h•L-1 (d
7), with an accumulation factor of 2.3±0.6 (P},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3536}
}