Pharmacokinetics Of Asiaticoside In Sd Rats

Objective: To investigate the pharmacokinetics(PK) of asiaticoside in rats and obtain the main pharmacokinetics parameters, tissue distribution and the mean cumulative excretion by HPLC methods to establish for determination of asiaticoside in rat plasma, tissue, bile, urine ,and feces.Methods: HPLC methods with UV detection were developed to study the pharmacokinetics of asiaticoside in SD rats . The chromatography condition were:Welchrom—C18 column(250mm×4.6mm,5um);Water–acetonitrile (24:76) as mobile phase at 1.0 mL·min-1; Detection wavelength was 221 nm. Plasma concentrations of asiaticoside were determined at different times after rats was given (iv) three different doses of asiaticoside(14,42,126 mg?kg-1), and the main parameters were calculated according to the 3P97 pharmacokinetic program. After single intravenous injection dose of asiaticoside(42 mg?kg-1), the rats were sacrificed at 5, 30 and 80 minutes and the tissues were obtained to detect. Meanwhile, the bile, urine, feces of rats were collected to dectect and get the mean cumulative excretion of asiaticoside.Results: In the chromatography condition, the rentention time of asiaticosid and cucurbitacin B were 6.04 and 8.12min, respectively. The mean extraction recoveries of plasma were 90.9%~94.7% and the mean relative recoveries were 99.0%~99.9%.The RSD of precision were 0.09%~6.14%. The asiaticoside pharmacokinetics conforms to a two-compartment open model after single iv does of asiaticoside 14 mg·kg-1,42mg·kg-1 or 126 mg·kg-1 in SD rats. The main parameters of three groups were as follows: T1/2αwere 1.75 ,1.89 and 1.73min, T1/2βwere27.14, 27.08 and 26.81min, K21 were 0.25, 0.24 and 0.20min-1, K10 were 0.039,0.039 and 0.031min-1, K12 were 0.13, 0.11 and 0.13min-1, area under the curve(AUC) were 471.32 , 1442.11and 5749.78 mg·min·L-1, clearance (CL) were 0.029, 0.029 and 0.022ml·g-1·min-1, MRT were 39.15, 39.08 and 38.70min, respectively. After a single iv dose of 42mg·kg-1 asiaticoside in rats, parent drug was distributed extensively and mainly distributed in heart ,liver, brain, spleen, lung and kidney. The peak levels were attained at 5min and decreased obviously at 80min after dosing in most tissues . Same times, the excretion of the parent drug in bile, urine and feces amounted to 27.11%, 2.213% and 2.545% of the dose at 24 h after a single iv dose of 42mg·kg-1 asiaticoside in rats, respectively.Conclusion: The pharmacokinetics of asiaticoside after iv administration showed a rapid distribution and elimination process in SD rats and was of first order kinetics. Parent drug was mainly distributed in heart ,liver, brain, spleen, lung and kidney. The parent drug excretion was only 30% of the dose mainly via bile at 24h after dosing.