Pharmacokinetics Of Saffloside A In Rats

OBJECTIVE In this work, the concentration-time course,tissue distribution ,excretion and plasma protein binding ratio of saffloside A in rat were investigated to provide pharmacokinetics parameters for its safe and rational clinical application.METHODS RP-HPLC method was employed to determine the plasma protein binding ratio and concentratioin of saffloside A in tissue and fluid at different times after iv administration in rats. And the pharmacokinetics parameters were acquired by statistic analyses. RESULTS The concentration-time course of saffloside A in rats were observed to be in accord with linear kinetics after i.v 3,6,12 and 24 mg/kg four dosages .And the concentration-time processes were found to fit a three-compartment open model at the dosage of 3 mg/kg,but a two-compartment open model was more suitable at the dosages of 6,12 and 24 mg/kg .The elimination half-lives(T1/2β) were 0.69 ± 0.31, 0.73 ±0.16, 0.55 ±0.07和 0.84±0.32h , the area under curves(AUC0-T) were 11.76±2.78,30.82±7.75,61.04±6.54和 153.31 ±60.49 mg/L*h,respectively .The area under curves(AUC0-T) were linearly related to the dosages (r=0.9961,P<0.05). Mean residence time (MRT0-tn) of four dosages was 0.76±0.12, 0.84±0.15 0.75±0.08 和 0.84±0.14h by noncompartmental analyses(the statistcal moment method) ,respectively. After iv 6mg/kg of saffloside A in rats , the drug could be detected in most tissues . At ten minutes after iv administration ,top tissue content was found in kidney ,plasma and bladder ;lung ,ovary ,large intestin and small intestin took second place ,and the lowest tissue content was detected in brain .The concentration in kidney was still in the highest level at 1,2and 4 hours.Other tissue content decreased largely with the exception of blind gut and large intestin at 4 hours.The total excretion of parent drug in urine and faeces was 52.4% and 6.2 % of the dose respectively. 53.4 % and 54.6% of saffloside A in plasma was shown to combined with plasma protein at concentration of 10 and 20μg/ml.CONCLUSION Saffloside A was eliminated more quickly and mainly excretedfrom kidney in manner of prototype without accumulation.The highest concentration was in kidney while the lowest one was in brain .