盐酸地尔硫缓释片在健康人体内的药动学和生物等效性研究

Pharmacokinetics and bioequivalence of diltiazem hydrochloride sustained release tablets in healthy volunteers

目的研究盐酸地尔硫受试制剂和参比制剂的人体药动学和生物等效性。方法单剂量试验组:18名健康受试者随机交叉口服受试制剂和参比制剂,剂量为120 mg。多剂量组:18名健康受试者随机交叉连续口服受试制剂和参比制剂60 mg(bid,连续7 d)。血样经预处理后采用HPLC紫外检测法测定地尔硫浓度,以计算其主要药动学参数并进行统计学分析。结果单剂量口服120 mg盐酸地尔硫后,受试制剂和参比制剂的各主要药动学参数如下:AUC0~t分别为(901.71±270.84)和(926.82±277.02)ng.h.mL-1,AUC0~∞分别为(974.58±292.88)和(995.85±291.13)ng.h.mL-1,Cmax分别为(97.66±26.36)和(101.78±33.54)ng.mL-1,tmax分别为(3.4±0.8)和(3.4±1.0)h。以AUC0~t计算受试制剂的相对生物利用度为(97.5±10.2)%。多剂量口服盐酸地尔硫60 mg达稳态后,受试制剂和参比制剂的各主要药动学参数如下:AUCs0s^t分别为(803.42±205.68)和(783.22±181.62)ng.mL-1,AUCss分别为(566.67±128.14)和(549.59±112.58)ng.h.mL-1、Csmsax分别为(84.07±21.12)和(79.09±19.12)ng.mL-1、Csmsin分别为(27.34±5.81)和(27.21±5.02)ng.h.mL-1、Cav分别为(47.222±10.678)和(45.799±9.381)ng.mL-1、tmax分别为(3.0±0.3)和(3.1±0.4)h、DF分别为(1.19±0.26)和(1.12±0.24),以AUC0ss^t计算的受试制剂的相对生物利用度为(102.6±12.5)%。结论经方差分析及双单侧t检验结果显示受试制剂和参比制剂具有生物等效性。

Objective To determine the pharmacokinetics and bioequivalence of dihiazem hydrochloride test and reference preparation in healthy volunteers. Methods In the single dose study, 120 mg of the test or the reference preparation was given to 18 healthy volunteers in a randomized two-period crossover study. In the multiple dose study, another 18 volunteers received dihiazem hydrochloride test or reference preparation for 7 days （60 mg, bid）. Diltiazem concentration in the plasma was determined by HPLC-UV. Main pharmacokinetic parameters were calculated and compared by statistic analysis. Results The pharmacokinetic parameters of test and reference preparation obtained from the single dose study were as follows： AUG0-t was （901.71± 270.84 ） and （926.82 ± 277.02） ng · h · mL^-1, AUG0-t was （974.58±292.88） and （995.85±291.13） ng · h · mL^-1, Cmax was （97.66±26.36） and （101.78± 33.54） ng · mL^-1, tmax was （3.4±0.8） and （3.4±1.0） h, respevtively. The relative bioavalability of the test preparation was （97.5±10. 2）%. In the multiple dose study, the pharmacokinetic parameters were as follows： AUC0-t^ss, was （803.42±205.68） and （783.22±181.62） ng · mL^-1, AUC^ss was （566.67±128.14） and （549.59±112.58） ng·h · mL^-1 , Cmax^ss was （84.07±21.12） and （79.09±19.12） ng · mL^-1 , Cmin^ss was （27.34±5.81） and （27.21±5.02） ng·h · mL^-1, Cav was （47.222±10.678）and （45.799±9.381） ng·mL^-1, tmax was （3.0±0.3） and （3.1±0.4） h , DF was （1.19±0. 26） and （1.12±0. 24）, respectively. The relativebioavalability of the test preparation was （102.6±12.5）%. Conclusion Analysis of variance and two one-sided t tests show that the test and reference preparation are bioequivalent.