Aristolochic Acid I In Rats In Vivo Pharmacokinetic Studies

Before the research we read a lot of literatures and wrote some reviews about the advances in studies on pharmacokinetics of aristolochic acid I, aristolochic acid nephropathy and the therapy of aristolochic acid nephropathy.Aristolochic acid (AA) we used was isolated from Aristolochiae manshuriensia Kom., and the concentration of Aristolochic acid I(AA-I) is 73.6%. A HPLC method was established for the determination of AA-I in AA, and there was no aristololactam I(AL-I) in the AA. AL-I (purity>98%) was synthesized and purified by our research group. Another HPLC method was also established for the determination of AA-I and AL-I in blood plasma, urine and kidney of rats. The results indicated that this method could be used to this experiment. The pharmacokinetic parameters were estimated by 3P97 program. The plasma AA-I and AL-I concentration-time curve were fit with the open two-compartment model and one-compartment model, respectively. The LC-MS was used to measure the AA-I and AL-I in the sample to make sure the result.The concentration of AA-I and AL-I in kidney rose suddenly after stopping administration for a long time. It indicated that maybe AA-I and AL-I store in other forms or other organs that cannot be determined in this method, and appeared suddenly after stopping administration for a long time. The result of our research clewed that maybe AA-I was capacity-limited drug .The metabolism of AA-I may need some saturation enzyme, carrier, or albumen, and this needed further study.The parameters about the blood picture, GOT, GPT, BUN and CRE of the rats were measured. Meanwhile some research of pathology about the stamoch, liver and kidney of the rats were done. The result indicated that there were some relationships between them. Maybe with further research, we can measure the parameters about the blood picture, GOT, GPT, BUN and CRE of the rats to help the diagnosis and therapy of aristolochic acid nephropathy.