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, FGFC1(2) (fungi fibrinolytic compound 1), were investigated in Wistar rats after intravenous (IV) bolus administration of two concentrations (10 and 20mg/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), 1.0mL/min. Chromatograms were monitored at 265nm (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±2.11min for 10 and 20mg/kg, respectively. AUC0-t were 412.19±19.09, 899.09±35.86μg/mLmin, 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±1.40min at 10 and 20mg/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 60min after administration, suggesting that enterohepatic circulation may exist.
College of food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Tongwei
T
Su
Wenhui
W
Wu
Ting
T
Yan
Chaoyan
C
Zhang
Quangang
Q
Zhu
Bin
B
Bao
D061605:Administration, Intravenous; D000818:Animals; D001685:Biological Factors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008099:Liver / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013191:Stachybotrys / Q000737:chemistry; D014018:Tissue Distribution
D001685:Biological Factors; D005343:Fibrinolytic Agents
Fibrinolytic compound; HPLC; Pharmacokinetic characters; Tissue distribution