目的研究环维黄杨星D在健康受试者中的人体药动学。方法32名健康受试者随机分为6,4,2mg 3个单剂量组及2mg 1个多剂量组,每组8人,静脉滴注环维黄杨星D2,4,6mg以及多次静脉滴注环维黄杨星D 2mg后,用高效液相色谱-质谱联用技术测定血浆中环维黄杨星D浓度。结果单剂量静脉滴注环维黄杨星D高、中、低剂量组的ρ_max分别为(16.56±1.15),(9.227±2.204)和(4.742±1.607)μg·L^-1;t_max分别为(1.625±0.551),(1.917±0.691)和(1.583±0.731)h。低剂量组多次静脉滴注后的ρ_max和t_max分别为(5.252±2.078)μg·L^-1和(1.786±0.267)h,平均稳态血药浓度ρ_av为(4.972±1.038)μg·L^-1。波动系数DF为(0.902±0.477),累积系数R为(2.629±1.187)。结论健康受试者单次静脉滴注高、中、低3个剂量组的环维黄杨星D后,药动学参数t_max,K,t_1/2,MRT相近,ρ_max,AUC_0→∞与剂量呈依赖性。药物半衰期较长,多剂量在体内有蓄积现象。

OBJECTIVE To study the pharmacokinetics of cyclovirobuxine D in healthy volunteers.METHODS 32 Healthy volunteers were randomly divided into four pools,Each of which consisted of 8,and were administered 6,4 and 2 mg of cyclovirobuxine D by intravenous drip in three single-dose groups and 2 mg in a multiple-dose group,respectively.After plasma sampling,plasma concentration of cyclovirobuxine D was determined by LC/MS/MS.RESULTS After a single infusion dose of 6,4 and 2 mg of cyclovirobuxine D,the pharmacokinetic parameters were as follows:ρ_max(16.56±1.15),(9.227±2.204) and(4.742±1.607)μg·L^-1;t_max(1.625±0.551),(1.917±0.691) and(1.583±0.731)h.After multiple doses of 2 mg cyclovirobuxine,ρ_max and tmax were found to be(5.252±2.078)μg·L^-1 and(1.786±0.267)h.ρ_av was estimated to be(4.972±1.038)μg·L^-1.Degree of fluctuation(DF) was(0.902±0.477),and accumulation coefficient(R) was(2.629±1.187).CONCLUSION For the three groups received a single dose of 6,4 and 2 mg of cyclovirobuxine D respectively,pharmacokinetic parameters,such as t_max,K,t_1/2,MRT,were similar while ρ_max and AUC_0→∞ were dose-dependented.The half life of cyclovirobuxine D in vivo was quite long,and an obvious cumulation was observed in the multiple-dose group.