摘要
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：AUC0→t分别为（1 074.45±381.54）和（1 159.30±447.82）μg·L^-1,AUC0→∞分别为（1 289.20±497.36）和（1 339.97±432.22）μg·L^-1;ρmax分别为（243.89±101.09）和（271.25±128.54）μg·L^-1;tmax分别为（2.24±1.64）和（1.98±1.35）h。AUC0→t90%可信限为82.7%～106.4%,AUC0→∞90%可信限为84.2%～107.6%;ρmax90%可信限为77.7%～105.7%,tmax经秩和检验无显著性差异（P〉0.05）,受试制剂与参比制剂以AUC0→t与AUC0→∞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：AUC0→t、AUC0→∞和ρmax均接受受试制剂与参比制剂生物等效性的假设,tmax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。
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 pharmacokinetie parameters of the two preparations were as follows ： ρmax （243.89±101. 09） and （ 271.25 ± 128.54 ） μg·L^-1. tmax （ 2.24±1.64 ） and （ 1.98±1.35 ） μg·L^-1. The AUC0-t and AUC0-∞ 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.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2008年第12期929-932,共4页
Chinese Pharmaceutical Journal
关键词
茴三硫
去甲茴三硫
药动学
生物等效性
高效液相色谱法
anethol trithione
demethyl-anethol trithione
pharmaeokinetics
bioequivalenee
high performance liquid chromatography
