Pharmacokinetics and tissue distribution of a novel marine fibrinolytic compound in Wistar rat following intravenous administrations

We investigated a novel marine fibrinolytic compound for use in thrombolytic therapy. Pharmacokinetics and the tissue distribution of this novel marine fibrinolytic compound, FGFC122 Fungi fibrinolytic compound 1,2,5-bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-tertahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid, a novel pyran-isoindolone derivative with bioactivity isolated from marine microorganism in our laboratory. i fibrinolytic compound 1), were investigated in Wistar rats after intravenous (IV) bolus administration of two concentrations (10 and 20 mg/kg). Plasma FGFC1 and tissue extracts were measured using HPLC with UV detection. FGFC1 was detected using a C18 column with a gradient eluted mobile phase of acetonitrile–water (0.1% trifluoroacetic acid), 1.0 mL/min. Chromatograms were monitored at 265 nm (column temperature: 40 °C). Pharmacokinetic data indicate that FGFC1 fitted well to a two-compartment model. Elimination half-lives (t1/2) of FGFC1 were 21.51 ± 2.17 and 23.22 ± 2.11 min for 10 and 20 mg/kg, respectively. AUC0 - t were 412.19 ± 19.09, 899.09 ± 35.86 μg/mL min, systemic clearance (CL) was 0.023 ± 0.002, 0.022 ± 0.002 ((mg/kg)/(μg/mL)/min) and the mean residence time (MRT) was 10.15 ± 0.97, 9.65 ± 1.40 min at 10 and 20 mg/kg, respectively. No significant differences were observed in the systemic clearance and mean residence time at the tested doses, suggesting linear pharmacokinetics in rats. Tissue distribution data reveal that FGFC1 distributed rapidly in most tissues except the brain and that the highest concentration of the drug was in the liver. In the small intestine, FGFC1 initially increased and then declined, but remained comparatively high 60 min after administration, suggesting that enterohepatic circulation may exist