Pharmacokinetics Study of PELGE-crebanine Nanoparticles in Rabbits / 中国药房

ABSTRACT

OBJECTIVE：To stud y the pharmacok inetics of PELGE-crebanine nanopartic les （PELGE-Cre-NPs） in rabbits. METHODS：Totally 6 rabbits were collected ，and injected with PELGE-Cre-NPs （3.5 mg/kg）via ear vein. 1 mL of blood samples were collected at 5，15，30，60，90，120，150，180，240，300 min after administration from the ear vein. After the plasma were isolated and Cre were extracted with ethyl acetate ，HPLC method was adopted to determine the plasma concentration of Cre by using verapamil hydrochloride as internal standard. The plasma concentration-time curve was drawed and pharmacokinetic parameters were calculated by using DAS 2.0 software. Chromatographic conditions such as the chromatographic column was Agilent ZORBAX Extend-C 18；the mobile phase consisted of methanol- 0.01％ triethylamine solution （75 ∶ 25，V/V）；the flow rate was 1 mL/min；the detection wavelength was 280 nm；the column temperature was 30 ℃；the injection volume was 20 μL. RESULTS：The linear range of Cre were 45.0-3 600 µg/L（R2＝0.999 9）. RSDs of inter-day and intra-day precision and stability tests were all lower than 5％（n＝6 or n＝12）；the accuracies were （97.44±2.41）％-（98.45±3.87）％（n＝6）. PELGE-Cre-NPs was in a two-compartment model in rabbits. Main pharmacokinetic parameters included that t1/2 was（109.357±33.917）min；CL was（0.016±0.001）L/（min·kg）；MRT was （76.733±7.502）min；cmax was（3 699.458±287.713）μg/L. CONCLUSIONS：The half-life period of PELGE-Cre-NPs in rabbits is longer than that of Cre injection；its retention time in the body is prolonged ，and sustained-release effect is obvious.