title: Pharmacokinetics of PEGylated recombinant human endostatin (M2ES) in rats.
abstract: OBJECTIVE
  M2ES is PEGylated recombinant human endostatin. In this study we investigated the pharmacokinetics, tissue distribution, and excretion of M2ES in rats.
  
  
  METHODS
  (125)I-radiolabeled M2ES was administered to rats by intravenous bolus injection at 3 mg/kg. The pharmacokinetics, tissue distribution and excretion of M2ES were investigated using the trichloroacetic acid (TCA) precipitation method.
  
  
  RESULTS
  The serum M2ES concentration-time curve after a single intravenous dose of 3 mg/kg in rats was fitted with a non-compartment model. The pharmacokinetic parameters were evaluated as follows: Cmax=28.3 μg·equ/mL, t1/2=71.5 h, AUC(0-∞)=174.6 μg·equ·h/mL, Cl=17.2 mL·h(-1)·kg(-1), MRT=57.6 h, and Vss=989.8 mL/kg for the total radioactivity; Cmax=30.3 μg·equ/mL, t1/2=60.1 h, AUC(0-∞)=146.2 μg·equ·h/mL, Cl=20.6 mL·h(-1)·kg(-1), MRT=47.4 h, and Vss=974.6 mL/kg for the TCA precipitate radioactivity. M2ES was rapidly and widely distributed in various tissues and showed substantial deposition in kidney, adrenal gland, lung, spleen, bladder and liver. The radioactivity recovered in the urine and feces by 432 h post-dose was 71.3% and 8.3%, respectively. Only 0.98% of radioactivity was excreted in the bile by 24 h post-dose.
  
  
  CONCLUSIONS
  PEG modification substantially prolongs the circulation time of recombinant human endostatin and effectively improves its pharmacokinetic behavior. M2ES is extensively distributed in most tissues of rats, including kidney, adrenal gland, lung, spleen, bladder and liver. Urinary excretion was the major elimination route for M2ES.
authors.affiliation: China's National Center for Safety Evaluation of Drugs, Beijing 100050, China.
authors.forename: Zuo-gang
authors.initials: ZG
authors.lastname: Li
authors.affiliation: 1] National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084, China [2] Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, China [3] Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jia
authors.affiliation: 1] Peking Union Medical College, Tsinghua University, Beijing 100084, China [2] National Institutes for Food and Drug Control, Tsinghua University, Beijing 100084, China.
authors.forename: Li-fang
authors.initials: LF
authors.lastname: Guo
authors.affiliation: China's National Center for Safety Evaluation of Drugs, Beijing 100050, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: China's National Center for Safety Evaluation of Drugs, Beijing 100050, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.affiliation: China's National Center for Safety Evaluation of Drugs, Beijing 100050, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Nie
authors.affiliation: 1] National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084, China [2] Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, China [3] Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.affiliation: National Institutes for Food and Drug Control, Tsinghua University, Beijing 100084, China.
authors.forename: Chun-ming
authors.initials: CM
authors.lastname: Rao
authors.affiliation: National Institutes for Food and Drug Control, Tsinghua University, Beijing 100084, China.
authors.forename: Jun-zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: 1] National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084, China [2] Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, China [3] Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yong-zhang
authors.initials: YZ
authors.lastname: Luo
mesh_terms: D000818:Animals; D043169:Endostatins / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D043169:Endostatins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols