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目的:研究中国健康成年男性志愿者单次口服伐地那非片剂的药动学。方法:按GCP指导原则设计试验方案,选择32例受试者随机分组,分别口服5,10,20和40mg四个剂量的伐地那非片剂。应用LC／MS／MS方法测定血浆和尿样中伐地那非浓度并计算药动学参数。结果:血浆和尿样中伐地那非浓度线性范围分别为0.10-50.00和0.25-50.00μg·L-1,最低检测浓度分别为0.10和0.25μg·L-1,回收率分别在101.2％-114.7％和90.40％-103.44％,日内日间变异系数分别小于10％和6％。受试者分别服用5,10,20和40mg的伐地那非后,血药浓度-时间曲线符合二房室模型,各剂量组间主要药动学参数Tmax,Ka,V／F(c),t1(?)α,MRT0-t,MRT0-∞,CL(s)差异无显著性,t1(?)β,Ke除40mg组与其他组有差异外,其他组间差异无显著性。AUC0-1,AUC0-∞,Cmax随剂量增加显著增加。各剂量组归一化后AUC0-t／dose,AUC0-∞／dose,Cmax／dose比较差异无显著性。各剂量组尿液中48h累积排出百分比小于1.5％。结论:伐地那非血药浓度-时间曲线符合二房室模型,在5-40mg之间基本呈现线性药动学特征。
Objective: To study the pharmacokinetics of a single oral dose of vardenafil in healthy male volunteers in China. Methods: According to the guidelines of GCP, the experimental protocol was designed and 32 subjects were randomized to receive 5, 10, 20 and 40 mg of vardenafil orally. The concentration of vardenafil in plasma and urine samples was determined by LC / MS / MS and the pharmacokinetic parameters were calculated. Results: The linear range of vardenafil concentrations in plasma and urine samples were 0.10-50.00 and 0.25-50.00 μg · L-1, respectively. The minimum detectable concentrations were 0.10 and 0.25 μg · L-1, respectively, and the recoveries were 101.2% 114.7% and 90.40% -103.44% respectively. The intra-day and inter-day coefficient of variation were less than 10% and 6% respectively. After taking 5, 10, 20 and 40 mg of vardenafil respectively, the blood concentration-time curves were in accordance with the two-compartment model. The main pharmacokinetic parameters Tmax, Ka, V / F t1 (?) α, MRT0-t, MRT0-∞ and CL (s) were not significantly different between the two groups. There was no significant difference between the other groups except t1 (?)? AUC0-1, AUC0-∞, Cmax increased significantly with dose. There was no significant difference in AUC0-t / dose, AUC0-∞ / dose and Cmax / dose after normalization in each dose group. Urine 48h cumulative discharge percentage of each dose group is less than 1.5%. CONCLUSION: The vardenafil plasma concentration-time curve conforms to the two-compartment model and basically exhibits linear pharmacokinetic characteristics between 5-40 mg.