Pharmacokinetics, tissue distribution and excretion of porcine fibrinogen after intraperitoneal injection of a porcine-derived fibrin glue to rats.
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.
Xie
Ying
Y
Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, PR China.
Zhong
Gaoren
G
He
Hongbing
H
Fan
Guorong
G
Wu
Yutian
Y
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
D007457:Iodine Radioisotopes; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril; D014508:Urea; D005337:Fibrin; D005340:Fibrinogen