The Pharmacokinetics Study Of DYSP-C07

Photodynamic therapy（PDT）is an innovative therapeutic approach which has been increasingly applied in clinical cancer therapy.DYSP-C07 prepared from the raw material Chenghai Chlorin（CHC）,which is extracted from spirulina powder of Chenghai Lake,is a novel chlorin-type compound with effective antitumor activity in PDT.The pharmacokinetic behavior of DYSP-C07 was studied before the pharmacodynamics evaluation.The high performance liquid chromatography（HPLC）method is convenient to detect the prototype drug,therefore HPLC method is used to elucidate the pharmacokinetic properties of DYSP-C07 in SD rats,and investigate the accumulation in the tissues of ICR tumor-bearing mice,providing the basis for the continuous administration time and photodynamic therapeutic time of the pharmacodynamics study.Firstly,HPLC method was applied to test inter and intro-day precision and accuracy and stability assay（room temperature storage,low temperature storage,repeated freezing-thawing）of plasma samples.The results showed that the inter and intra-day precision of plasma samples was less than 15%,and the accuracy was within±20%,which conform to the fourth part of the 2015 edition of Chinese Pharmacopoeia for biological analysis samples.The extraction rates of DYSP-C07 in plasma with high,medium,low and lowest detection limit concentrations were 65.89±2.38%,69.71±0.22%,74.39±1.13%and 80.73±0.35%,respectively,and the extraction rate of internal standard was 68.10±0.99%.Based on the verified quantitative analysis method,it was determined that DYSP-C07 in SD rats conforms to the two-compartment model,and the distribution half-life(t_1/2α)and the elimination half-life(t_1/2β)was 0.627±0.256 h and 7.421±0.802 h,respectively.In addition,the binding rates between high,medium and low concentrations of DYSP-C07 and plasma protein determined byequilibrium dialysis method were 90.94±1.90%,92.25±1.40%and 95.78±1.20%,respectively.DYSP-C07 can be detected in the heart,liver,spleen,lung,kidney and tumor of ICR tumor-bearing mice.In addition,DYSP-C07 kept a high concentration in the liver and kidney tissue,and the compound gradually accumulated in tumor,maintaining a high level of aggregation in the range of 6 h～12 h.In this study,the pharmacokinetic process of DYSP-C07 in SD rat was consistent with two-compartment model,and it was highly binding to the SD rat plasma protein.DYSP-C07also showed a high degree of aggregation in the liver and kidney tissue of ICR tumor-bearing mice,and could be concentrated in the tumor tissue.After intravenous administration,the pharmacokinetics and tissue distribution of DYSP-C07 in mice were detected by established high performance liquid chromatography with ultraviolet detection method.It is suggested to take 7 h the elimination half-life time of DYSP-C07 as the initial photodynamic therapeutic time in the pharmacodynamics study.