title: Pharmacokinetics, distribution, and excretion of 125I-labeled human plasma-derived-FVIIa and -FX with MC710 (FVIIa/FX mixture) in rats.
abstract: BACKGROUND
  MC710 is a mixture agent consisting of plasma-derived activated factor VII (FVIIa) and factor X (FX) at a weight ratio of 1:10 developed as a novel bypassing agent for the management of the bleeding of hemophilia patients with inhibitors. The pharmacokinetics, distribution, and excretion of (125)I-labeled-FVIIa ((125)I-FVIIa) and -FX ((125)I-FX) were studied in male rats after a single intravenous administration of (125)I-FVIIa or (125)I-FX combined with MC710.
  
  
  METHODS
  (125)I-FVIIa or (125)I-FX was administered intravenously with MC710 to male rats in a single dosage (FVIIa 0.4 mg and FX 4 mg/kg body weight) and radioactivity and antigen levels in plasma were quantified for 24h. Urine and feces were sampled to study the excretion of radioactivity during 168 h after dosing. Whole-body autoradiography was performed to evaluate the qualitative distribution of radioactivity 168 h after dosing.
  
  
  CONCLUSIONS
  The half-life (t(1/2)α and t(1/2)β) of radioactivity and FVIIa antigen were 0.704 and 6.27 h, and 0.496 and 1.66 h, respectively and the area under the plasma concentration-time curve (AUC(0-∞)) of radioactivity and FVIIa antigen were 17,932 and 8671 ng·h/mL, respectively. The t(1/2) of radioactivity and FX antigen were 4.06 and 3.05 h, respectively, and the AUC(0-∞) of radioactivity and FX antigen were 320,143 and 395,794 ng·h/mL, respectively. About 80% of the administered dose of radioactivity was excreted in urine and feces by 168 h after administration. Tissue distribution experiments showed that FVIIa- and FX-related (125)I accumulated in bone and bone marrow, and disappeared slowly.
authors.affiliation: Therapeutic Protein Product Research Department, The Chemo-Sero-Therapeutic Research Institute, KAKETSUKEN, Kumamoto, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakatomi
authors.forename: Manami
authors.initials: M
authors.lastname: Tsuji
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Nakashima
authors.forename: Soutaro
authors.initials: S
authors.lastname: Gokudan
authors.forename: Hiroki
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tomokiyo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ogata
authors.forename: Satomi
authors.initials: S
authors.lastname: Harano
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsui
authors.forename: Takamichi
authors.initials: T
authors.lastname: Shigaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mogi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001853:Bone Marrow / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D003029:Coagulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D015942:Factor VIIa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D005170:Factor X / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D014018:Tissue Distribution
chemical_list: D003029:Coagulants; D004338:Drug Combinations; D007457:Iodine Radioisotopes; C000588640:MC710; D005170:Factor X; D015942:Factor VIIa