fibrin and 1-3-4-6-tetrachloro-3-alpha-6-alpha-diphenylglycoluril

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.

Topics: Animals; Area Under Curve; Chemistry, Pharmaceutical; Female; Fibrin; Fibrinogen; Injections, Intraperitoneal; Iodine Radioisotopes; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Swine; Tissue Distribution; Urea