Studies On Pharmacokinetics Of Andrographolide Derivative ISA

Andrographis paniculata(Burm.f.)Nees was found in India and planted in east, middlesouth and southwest China. It is used extensively as an antipyretic, anti-inflammtory and antivirus medicine for a long time. Recently, it's newly pharmacological activities were found, has strongly anti-tumour effect. ISA,a derivative of andrographolide,which synthesised by our group.We detected ISA blood concentration in different time after iv and ig ISA by the method of HPLC . The pharmacokinetic parameters of T1/2α,T1/2β,Cmax,tmax,AUC are 1.34h,4.42h,1.76h,106.06μg/mL,540.59μg/mL·h respectively after i.g ISA and the The pharmacokinetic parameters of T1/2α,T1/2β,AUC are 67.85min,185.45min,489.21μg/mL·h respectively after i.v ISA.The method of superfilter was developed to detect the plasma protein binding rate,when the concentration of ISA are 0.077μg/mL,0.114μg/mL and 0.186μg/mL,the plasma protein binding rate are 25.42%,28.64% and 28.45%respectively .The mean binding rate is 27.5%.The drug concentration in heart,liver,spleen,lung,kindy of mice was detected after iv ISA 5min,20min,40min,60min,90min by the method of HPLC.And the outcome shows that the content of ISA is higher in the tissues of liver,heart,lung,kindy.The concention of ISA is lowest in fat.As the mentiond above ,after ISA was given iv and ig to rats ,the pharmacokinetics process conform to the two-compartment model and elimination of first-order kinetics.The absolute bioavailability of ISA was 14.59%; The Plasma protein binding rate of ISA was less than 30%; ISA was distributed to all organs and the high concentration was detected in liver,lung,heart and kindy.