【摘要】 目的:研究中国健康成年男性志愿者单次口服D-聚甘酯片的药代动力学。方法:按GCP指导原则设计试验方案,选择9名健康成年男性志愿者,按拉丁方随机分组,依次分别口服400mg,500mg,600mg3个剂量的D-聚甘酯片。应用免疫荧光比浊法测定给药后不同时间点血浆的部分凝血活酶时间（aPTT）,据随行测定的aPTT-血浆浓度标准曲线,计算相应的血药浓度,采用3P97软件拟合药代动力学参数。结果:依据aPTT结果计算D-聚甘酯血浆浓度,在0.05～10mg·L-1浓度范围内呈良好的线性关系（r=0.9957）;最低检测浓度为0.05mg·L-1,回收率在91.48％～105.67％之间,日内日间变异小于13％。受试者分别口服D-聚甘酯片400mg,500mg,600mg后,血药浓度-时间曲线符合一级吸收、一级消除、二房室模型,各剂量组药代动力学参数α,β,κa,tmax,t1/2α,t1/2β,CL差异无统计学意义,AUC0-∞,AUC0-t,Cmax随剂量增加显著增加。各剂量组归一化AUC0-t/dose与Cmaz/dose比较差异无统计学意义。结论:9名健康受试者单次口服D-聚甘酯片400mg,500mg,600mg后,血药浓度-时间曲线符合二房室模型,在此剂量范围内体内过程符合线性动力学特征。更多还原

【Abstract】 OBJECTIVE: To investigate the pharmacokinetics of single dose D-polymannuronicate tablets in Chinese healthy volunteers. METHODS: The protocol was designed according to GCP principle .9 healthy volunteers were divided into 3 groups randomly by Latin method. The aPTT of plasma samples collected from the volunteers after taking orally 400mg, 500mg, 600mg D-polymannuronicate respectively by turns were determined by the immuno-fluorescence turbidity method. The plasma concentrations were determined by the accompanity aPTT-plasma concentration standard curve and the pharmacokinetcs parameters were calculated by 3P97 software. RESULTS: The well linearity(r=0.9957) in 0.05-10mg·L-1 of plasma concentrations with aPTT was found. The lowest limitation of the concentrations was 0.05 mg·L-1 and the recovery rate was from 91.48%-105.67%, the derivations within-day and between-days were less than 13%.The plasma concentration -time curve fit the first order absorption, the first order elimination,two compartment model after an oral dose D-polymannuronicate (400mg, 500mg, 600mg). There were no significant differences in pharmacokinetic parameters α, β,Ka,tmax,t1/2,t1/2 β,V/ F,CL between the three groups.But AUC0-∞,AUC0-t and Cmax increased with doserising. There were no significant differences in AUC0-∞/dose, AUC0-1/dose between the groups. CONCLUSION:The plasma concentration-time curve fits two compartment model in 9 healthy volunteers after taking single dose D-polymannuronicate (400mg, 500mg, 600mg) tablets and the process of the drug in human body fit linear dynamic feature.更多还原