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 Na125I using the Iodo-Gen method. Following the purification and identification of 125I-porcine fibrinogen, the fibrin glue containing 125I-porcine fibrinogen was intraperitoneally administered to rats at three single dosages (100, 200, 400 mg/kg of porcine fibrinogen). The results showed that the 125I-labeled assay method was suitable for the quantification of porcine fibrinogen in plasma samples, tissue samples and excreta samples with satisfactory linear (r2 > 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 tmax of 1.83–5.67 h and a slow elimination proceeding with the terminal elimination half-life (T1/2) of 84.5–96.3 h. Porcine fibrinogen was widely distributed to most of the tissues examined after a single intraperitoneal administration at 200 mg/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.