摘要
目的:建立人血浆中酮康唑的高效液相色谱-质谱测定方法。研究受试制剂酮康唑片在人体内的药代动力学特征,评价其相对生物利用度和生物等效性。方法:20名男性健康受试者随机分成2组,进行双交叉试验,受试及参比制剂剂量均为200 mg。采用高效液相色谱-质谱法测定血药浓度。结果:志愿者口服受试和参比制剂后,酮康唑的药动学参数如下:峰浓度分别为(4.77±1.63)μg.mL-1和(5.09±1.64)μg.mL-1,达峰时间分别为(1.37±0.71)h和(1.19±0.61)h,消除半衰期分别为(1.89±0.80)h和(2.13±0.91)h,平均驻留时间分别为(3.02±0.81)h和(3.04±0.81)h,AUC0-24分别为(13.03±5.65)μg.h.mL-1和(13.99±6.54)μg.h.mL-1;相对生物利用度为95.6%±12.5%。结论:建立的分析方法准确、灵敏、可靠、简便,统计结果表明受试制剂和参比制剂生物等效。
Objective： To develop an analytical method for the determination of ketoconazole in human plasma with HPLC-MS, to calculate the pharmacokinetie parameters and relative-bioavailability of ketoconazole, and to evaluate the bioequivalence of ketoconazole versus equal dose of NizoralTM in healthy volunteers. Methods： 20 male healthy volunteers participated in this study were divided into 2 groups randomly. After a single crossover oral dose of test or reference tablets containing 200 mg ketoconazole, the concentration of ketoeonazole in human plasma samples were determined by HPLCMS. Results： The main pharmacokinetic parameters were calculated with DAS 2.0 as follows C t t1/2, MRT and AUC0-24 of ketoconazole in test and reference tablets were ： （4. 77 ± 1.63 ） and （5.09±1.64）μg·mL^-1, （1.37±0.71） and （1.19±0.61） h, （1.89 ±0.80） and （2.13±0.91） h, （3.02 ±0.81） and （3.04± 0.81） h, （13.03±5.65） and （13.99±6.54） μg·h·mL^-1 , respectively. The relative-hioavailability of ketoconazole was （ 95.6%±12. 5% ）. Conclusion： The method is proved to be accurate, sensitive, reliable and simple. Ketoconazole in the test tablets is bioequivalent to the reference tablets.
出处
《药学与临床研究》
2009年第3期267-270,共4页
Pharmaceutical and Clinical Research
