The pharmacokinetic properties of LL6 were investigated in SD rats (n = 3). The left femoral artery and vein were catheterized with polyethylene tube (IntramedicTM PE-50; Becton-Dickinson Diagnostics, MD, USA) under Zoletil (Virbac, Carros, France) anesthesia (50 mg/kg, intramuscular injection). LL6 was dissolved in DMSO/PEG 400/normal saline mixture (35:35:30, v/v/v) and single dose solution (1 mg/kg) was administered to rat intravenously. Approximately 150 µL of blood samples were collected via femoral artery at predetermined time (1, 3, 5, 10, 15, 30, 60, 120 and 180 min) and equivalent volume of normal saline solution with 20 U/mL of heparin was replenished to prevent blood coagulation. After centrifugation of the sample at 16,000 × g for 5 min, 50 µL aliquot of plasma samples were stored at -20 °C until HPLC-MS/MS analysis. The Pharmacokinetic parameters, including terminal half-life (T½), area under the plasma concentration-time curve from time zero to time last (AUClast), area under the plasma concentration-time curve from time zero to time infinity (AUCinf), volume of distribution at steady-state (Vss) and mean residence time (MRT) were calculated using non-compartmental analysis (WinNonlin, version 3.1, NCA 201; Pharsight, Mountain View, CA, USA).

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