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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。
Objective: To study the pharmacokinetics of single oral D-polyglycerol tablets in healthy male volunteers in China. Methods: According to the guidelines of GCP, the experimental protocol was designed. Nine healthy adult male volunteers were selected and randomly divided into three groups according to the Latin prescriptions: D-polyglycerol tablets of 400mg, 500mg and 600mg respectively. The plasma thromboplastin time (aPTT) at different time points after administration was measured by immunofluorescence turbidimetry. According to the standard curve of aPTT-plasma concentration measured at the same time, the corresponding plasma concentration was calculated, and the pharmacokinetics were fitted by 3P97 software Learning parameters. Results: The plasma concentration of D-polyglycerol was calculated according to aPTT. The linear range was 0.05-10 mg · L-1 (r = 0.9957). The lowest concentration was 0.05 mg · L-1. The recovery was in the range of 91.48% ~ 105.67%, the intraday variation was less than 13%. After oral administration of D-polyglutamic acid tablets 400mg, 500mg and 600mg respectively, the blood concentration-time curve was in agreement with the first-order absorption and the first-order elimination. Two-compartment model and the pharmacokinetic parameters α, β, , tmax, t1 / 2α, t1 / 2β, CL had no statistical significance. The AUC0-∞, AUC0-t, Cmax increased with dose. Each dose group normalized AUC0-t / dose and Cmaz / dose difference was not statistically significant. CONCLUSION: The blood concentration-time curve of nine healthy subjects after single oral administration of D-polyglycerol tablets 400mg, 500mg and 600mg conforms to the two-compartment model. The in vivo process is in line with the linear kinetic characteristics.