茴三硫片人体药动学与生物等效性研究

 目的建立高效液相色谱法测定人血浆中茴三硫代谢产物的浓度,研究其在人体内的药动学和相对生物利用度,并进行生物等效性评价。方法采用2制剂双周期交叉试验设计。20名男性健康志愿者随机分别服用2种茴三硫片75 mg,采用高效液相色谱紫外法(HPLC-UV),以美洛昔康为内标测定血浆中茴三硫代谢产物去甲茴三硫浓度。采用DAS 2.0.1程序进行药动学参数计算,并对两种制剂作出等效性评价。结果建立血浆去甲茴三硫浓度的反相高效液相色谱测定法。单剂量口服75 mg茴三硫片受试制剂与参比制剂的药动学参数:AUC_0→t分别为(1 074.45±381.54)和(1 159.30±447.82)μg·L^-1,AUC_0→∞分别为(1 289.20±497.36)和(1 339.97±432.22)μg·L^-1;ρ_max分别为(243.89±101.09)和(271.25±128.54)μg·L^-1;t_max分别为(2.24±1.64)和(1.98±1.35)h。AUC_0→t 90%可信限为82.7%～106.4%,AUC_0→∞ 90%可信限为84.2%～107.6%;ρ_max 90%可信限为77.7%～105.7%,t_max经秩和检验无显著性差异(P>0.05),受试制剂与参比制剂以AUC_0→t与AUC_0→∞计算其相对生物利用度分别为(98.4±32.5)%和(100.5±39.7)%。结论经方差分析及双单侧t检验表明:AUC_0→t、AUC_0→∞和ρ_max均接受受试制剂与参比制剂生物等效性的假设,t_max经秩和检验无显著性差异(P>0.05),可判断两种制剂是生物等效的。本实验检测血浆中去甲茴三硫浓度,方法灵敏、准确、简单、快速,可满足药动学和生物利用度试验方法学的要求。

Pharmacokinetics and Bioequivalence of Anethol Trithione in Chinese Healthy Volunteers

OBJECTIVE To develop a high performance liquid chromatography method for the determination of anethol trithione metabolites called demethyl-anethol trithione in human plasma,to study the pharmacokinetics of anethol trithione and evaluate the bioequivalence of two preparations in healthy subjects.METHODS A single oral dose of 75 mg test preparation or reference preparation were given to 20 healthy male volunteers in an open randomized crossover design.Demethyl-anethol trithione concentrations in plasma were determined by a HPLC-UV method.The pharmacokinetic parameters and relative bioavailability were calculated by DAS2.0.1 program to evaluate the bioequivalence of the two preparations.RESULTS The main pharmacokinetic parameters of the two preparations were as follows: ρ_max(243.89±101.09) and(271.25±128.54)μg·L^-1.t_max(2.24±1.64) and(1.98±1.35)μg·L^-1.The AUC_0-t and AUC_0-∞ relative bioavailability were(98.4±32.5)% and(100.5±39.7)%.CONCLUSION The statistical analysis of the result shows that the two preparations are bioequivalence.