进口盐酸塞利洛尔片在健康志愿者的血药浓度与药效学相关性

Correlation of imported celiprolol hydrochloride between plasma concentration and pharmacodynamics in healthy volunteers

目的 :研究进口盐酸塞利洛尔片在健康志愿者体内的血药浓度、药物动力学及药效学 ,并考查血药浓度与药效学相关性。方法 :用反相高效液相色谱法测定进口盐酸塞利洛尔片在 9名受试者体内血药浓度 ,同时用 GP- 30 3血流动力学测定仪测量平均血压 (MAP)、心率 (HR)、每搏输出量 (SV)、体循环阻力 (TPR)。结果 :服药后 3.5 h血药浓度达高峰 ,4.0 h药效达高峰。 9名受试者的药物动力学参数 Ka 为 (1.43± 0 .72 ) h- 1 ,K为 (0 .2 3± 0 .0 5 ) h- 1 ,T1 / 2 K为 (3.5 6± 0 .6 1) h,tmax为 (3.6 2±0 .5 0 ) h,cmax为 (972± 2 16 ) ng/ml,AUC为 (46 0 6± 5 19) ng· h/ml。血药浓度与药效ΔMAP、ΔHR、ΔSV和Δ TPR的相关系数分别为 r1 =(0 .92 2 3± 0 .0 2 30 )、r2 =(0 .72 5 4± 0 .0 16 2 )、r3=(0 .834 2± 0 .0 2 0 3)、r4=(0 .8411± 0 .0 175 )。结论 :药效高峰滞后于血药浓度高峰 ,血药浓度与各药效指标相关性依次为 ΔMAP>Δ TPR>ΔSV>Δ HR。

AIM:To study the plasma concentrations, pharmacokinetics and pharmacodynamics of imported celiprolol hydrochloride in healthy volunteers,and examine the correlation between plasma concentrations and pharmacodynamics. METHODS: The plasma concentrations of imported celiprolol hydrochloride tablets in vivo were determined with high performance liquid chromatography,at the same time mean artery pressure(MAP), heart rate(HR), stroke volume(SV), total peripheral resister (TPR) were messured with GP 303 instrument. RESULTS: Plasma concentrations attained peak in 3 5 h after taking drugs, and drug effects attained peak in 4 h.The pharmacokinetic parameters of 9 subjects were as following: K a (1 43±0 72)h -1 , K (0 23±0 05)h -1 , T 1/2K (3 56±0 61)h, t max (3 62±0 50)h, c max (972±216)ng/ml, AUC ( 4 606 ±519)ng·h/ml. The correlation factors between plasma concentrations and drug effects as ΔMAP,ΔHR ΔSV and ΔTRP were r 1= 0 922 3 ± 0 023 0 ,r 2= 0 725 4 ± 0 016 2 ,r 3= 0 834 2 ± 0 020 3 ,r 4= 0 841 1 ± 0 017 5 . CONCLUSION: Drug effect peak delays after plasma concentrations peak,the degree of correlation between plasma concentrations and drug effects index is ΔMAP>ΔTRP>ΔSV>ΔHR.