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目的:评价地尔硫(艹卓)释胶囊在中国人体内的药代动力学特性。方法:对12名健康志愿者进行了国产盐酸地尔硫(艹卓)缓释胶囊单剂量和多剂量的体内药代动力学的研究,地尔硫(艹卓)及代谢产物N－去甲基地尔硫(艹卓)(Ma)和去乙酰基地尔硫(艹卓)(M1)的血药浓度采用高效液相色谱法测定。结果:国产盐酸地尔硫(艹卓)缓释胶囊在中国人体内的血药浓度曲线无论是单剂量还是多剂量均呈一级释放一级吸收的单室模型。主要动力学参数:单剂量试验,消除速率常数ke为0.094±0.027h-1;tmax为5.80±1.14h;Cmax为42.90±17.91μg·L-1;AUC0~∞54.20±246.41μg·h·L-1。多剂量试验:消除速率常数ke为0.080±0.028h-1;tmax为4.58±1.14h;Cmax为151.6±71.27μg·h·L-1;AUC0~rn分别为1271.1±574.1μg·h·L-1。Css’min为98.68±42.88μg·L-1;DF为37.80%±20.34%。结论:比较单剂量用药和多剂量用药的药代动力学参数,提示地尔硫卓多剂量用药可能在体内出现明显的蓄积,临床用药时应注意药物不良反应的监护。
Objective: To evaluate the pharmacokinetics of diltiazem capsules in Chinese. Methods: Twelve healthy volunteers were studied on single-dose and multi-dose in vivo pharmacokinetics of diltiazem hydrochloride sustained-release capsules. Diltiazem and its metabolite N-desmethyl Plasma concentrations of basal sulfur (Ma) and desacetyl diltiazem (Ml) were determined by high performance liquid chromatography. Results: The plasma concentration curve of domestic Diltiazem hydrochloride sustained-release capsules in Chinese showed a first-order single-compartment absorption model with single-dose or multiple-dose release. The main kinetic parameters: single-dose test, the elimination rate constant ke was 0.094 ± 0.027h-1; tmax was 5.80 ± 1.14h; Cmax was 42.90 ± 17.91μg · L-1; AUC0 ~ ∞ 54.20 ± 246.41μg · h · L -1. The multi-dose test showed that the elimination rate constant ke was 0.080 ± 0.028 h-1, the tmax was 4.58 ± 1.14 h, the Cmax was 151.6 ± 71.27 μg · h-1 and the AUC0-rn was 1271.1 ± 574.1 μg · h · L- 1. Css’min was 98.68 ± 42.88 μg · L-1; DF was 37.80% ± 20.34%. Conclusions: Comparing the pharmacokinetic parameters of single dose and multiple dose drugs, suggesting that diltiazem dose of drug may be significant accumulation in the body, clinical medication should pay attention to adverse drug reactions monitoring.