两种剂量盐酸地尔硫芯卓缓释胶囊在健康人体药动学及参数相关性

Pharmacokinetics of diltiazem hydrochloride sustained-release capsule in healthy volunteers

目的 :研究盐酸地尔硫芯卓 缓释胶囊在人体内药动学特性及其两种不同剂量的药动学参数变化规律。方法 :健康志愿者 12名 ,随机分组 ,单剂量口服 6 0 ,12 0mg盐酸地尔硫芯卓 缓释胶囊 ,采用反相高效液相色谱法测定不同时间的血药浓度 ,经3P87程序拟合 ,求算药动学参数。结果 :6 0、12 0mg地尔硫 芯卓 缓释胶囊在中国健康志愿者体内的药动学参数为Ka(2 .2±2 .1) ,(1.6± 1.2 )h-1;K(0 .0 45± 0 .0 0 78) ,(0 .0 5 4± 0 .0 15 )h-1;T1/2 Ka(0 .6 0± 0 .36 ) ,(0 .7± 0 .4)h ;T1/2 K(15 .8± 2 .7) ,(13.9± 4.4)h ;V(33.2± 11.9) ,(2 9.8± 11.8)L·kg-1;Cl(1.4± 0 .37) ,(1.5± 0 .5 )L·h·kg-1;Tmax(4 .8± 0 .9) ,(4 .6± 1.0 )h ;Cmax(2 8.9± 10 .8) ,(6 5 .6± 2 4.8)ng·ml-1;AUC(75 1.2± 2 11.1) ,(1487.4± 5 33.1) μg·h·L-1。结论 :经配对t检验 ,两剂量组间药动学参数差异无显著性 (P >0 .0 5 ) ,在研究剂量内表现为线性动力学。

OBJECTIVE To study the pharmacokinetics of diltiazem hydrochloride sustained-release capsule in healthy volunteers.METHODS 60mg and 120mg diltiazem hydrochloride sustained-release capsules were given orally in a single dose to 12 healthy volunteers in a cross-over way.The diltiazem concentrations in serum were determined by RP-HPLC.The pharmacokinetic parameters were fitted and calculated by 3P87 program. RESULTS The main pharmacokinetics parameters of diltiazem hydrochloride sustained-release capsules after oral 60mg,120mg were as follows :T 1/2 K a( 0.60± 0.356),( 0.7± 0.4)h;T 1/2 K( 15.8± 2.7),( 13.9± 4.4)h;V( 33.2± 11.9),( 29.8± 11.8)L·kg -1;Cl( 1.4± 0.4),( 1.5± 0.5)L·h·kg -1;T max( 4.8± 0.9),( 4.6± 1.0)h;C max( 28.9± 10.8),( 65.6± 24.8)ng·ml -1;AUC( 751.2± 211.1),( 1487.4± 533.1)μg·h·L -1.CONCLUSIONS The parameters such as T 1/2 K, K , T max ,C max/D 0 and AUC/D 0 etc.in two kinds of dosage had no significant difference(P> 0.05). It's pharmacokinetics were linear.