title: Pharmacokinetics, tissue distribution and excretion of porcine fibrinogen after intraperitoneal injection of a porcine-derived fibrin glue to rats.
abstract: The aim of the present study was to characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of porcine fibrinogen in rats after intraperitoneal injection of a porcine-derived fibrin glue. A sensitive and rapid isotope-labeled assay method was developed and validated for quantitative analysis in biological analysis. Porcine fibrinogen, the major composition of the fibrin glue, was radioiodinated with Na(125)I using the Iodo-Gen method. Following the purification and identification of (125)I-porcine fibrinogen, the fibrin glue containing (125)I-porcine fibrinogen was intraperitoneally administered to rats at three single dosages (100, 200, 400mg/kg of porcine fibrinogen). The results showed that the (125)I-labeled assay method was suitable for the quantification of porcine fibrinogen in plasma samples, tissue samples and excreta samples with satisfactory linear (r(2)>0.998), precision (<13%), accuracy (95.9-104.2%) and recovery (>85%). After three single administrations, plasma concentration profiles showed a slow absorption phase with the mean t(max) of 1.83-5.67 h and a slow elimination proceeding with the terminal elimination half-life (T(1/2)) of 84.5-96.3h. Porcine fibrinogen was widely distributed to most of the tissues examined after a single intraperitoneal administration at 200mg/kg to rats. The radioactive porcine fibrinogen showed substantial disposition in liver, kidneys, stomach and intestine. Approximately 79.3% and 17.2% of administered radioactivity were recovered in urine and feces within 528 h post-dosing, which indicated the major elimination route was urinary excretion.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Gaoren
authors.initials: G
authors.lastname: Zhong
authors.forename: Hongbing
authors.initials: H
authors.lastname: He
authors.forename: Guorong
authors.initials: G
authors.lastname: Fan
authors.forename: Yutian
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry* / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013552:Swine; D014018:Tissue Distribution; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D007457:Iodine Radioisotopes; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril; D014508:Urea; D005337:Fibrin; D005340:Fibrinogen