title: PEGylation of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) results in decreased uptake into rats and human liver.
abstract: OBJECTIVE
  Our aim was to investigate the effect of PEGylation on the uptake of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) into rat liver, kidney and spleen, and human liver.
  
  
  METHODS
  Copolymer of polyethyleneglycol allylmethylether and maleamic acid sodium salt with OCIF (poly(PEG)-OCIF) (0.5 mg/kg) was administered to rats and the concentrations of poly(PEG)-OCIF in the liver, kidney and spleen at 15 min after administration were measured by ELISA. For human liver uptake, the liver perfusion of OCIF and (3)H-labelled poly(PEG)-OCIF was conducted using fresh human liver block.
  
  
  RESULTS
  The tissue uptake of poly(PEG)-OCIF in rats was significantly lower compared with that of OCIF. In fresh human liver perfusion, (3)H-poly(PEG)-OCIF was rarely taken up into the liver. On the other hand, more than 50% of the perfused OCIF was taken up.
  
  
  CONCLUSIONS
  PEGylation of OCIF using poly(PEG) dramatically suppressed the uptake of OCIF into human liver as well as into rat liver and could be a promising approach for improving the pharmacokinetic and pharmacological effects of OCIF in the clinical setting.
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan. saito.motoko.zf@daiichisankyo.co.jp
authors.forename: Motoko
authors.initials: M
authors.lastname: Saito-Yabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kasuya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshigae
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Yamamura
authors.forename: Yukie
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nao
authors.initials: N
authors.lastname: Fukuda
authors.forename: Masashi
authors.initials: M
authors.lastname: Honma
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yano
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Okada
authors.forename: Akiko
authors.initials: A
authors.lastname: Okada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Eisuke
authors.initials: E
authors.lastname: Tsuda
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Ursula
authors.initials: U
authors.lastname: Höpner
authors.forename: Silvia
authors.initials: S
authors.lastname: Zaja
authors.forename: Juergen
authors.initials: J
authors.lastname: Mueller
authors.forename: Junichi
authors.initials: J
authors.lastname: Okada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurihara
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Okazaki
mesh_terms: D000818:Animals; D001692:Biological Transport; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008298:Maleates / Q000737:chemistry; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010052:Ovariectomy; D010477:Perfusion; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D050071:Bone Density Conservation Agents; D008298:Maleates; D053244:Osteoprotegerin; D011092:Polyethylene Glycols; D006493:Heparin; C008311:maleamic acid