Pharmacokinetics of recombinant human endostatin in rats

Xiao Xia Yang, Zen Ping Hu, Eli Chan, Wei Duan, Shufeng Zhou

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)565-576
Number of pages12
JournalCurrent Drug Metabolism
Volume7
Issue number6
DOIs
StatePublished - Aug 2006

Fingerprint

Endostatins
Pharmacokinetics
Rats
Radioactivity
Bile Ducts
Ducts
Urine
Plasmas
Tissue Distribution
Human Body
Feces
Bile
Intravenous Injections
Liver
Area Under Curve
Haplorhini
Half-Life
Animals
Spleen
Body Weight

Keywords

  • Allometric scaling
  • Elimination
  • Endostatin
  • Pharmacokinetics
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Pharmacokinetics of recombinant human endostatin in rats. / Yang, Xiao Xia; Hu, Zen Ping; Chan, Eli; Duan, Wei; Zhou, Shufeng.

In: Current Drug Metabolism, Vol. 7, No. 6, 08.2006, p. 565-576.

Research output: Contribution to journalArticle

Yang, Xiao Xia ; Hu, Zen Ping ; Chan, Eli ; Duan, Wei ; Zhou, Shufeng. / Pharmacokinetics of recombinant human endostatin in rats. In: Current Drug Metabolism. 2006 ; Vol. 7, No. 6. pp. 565-576.
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