论文部分内容阅读
建立人血浆罗红霉素高效液相色谱-质谱联用测定法(HPLC-MS),研究两种罗红霉素胶囊在健康人体内的药代动力学和生物利用度。36名健康青年男性志愿者,采用随机分组、双交叉自身前后对照试验设计,单剂口服150mg罗红霉素参比制剂或试验制剂,用HPLC-MS测定血浆中罗红霉素浓度变化。结果表明:经DAS2.0药动学程序处理,罗红霉素胶囊的平均药时曲线下面积(Area Under Concentration-time Cure,AUC)AUC(0～72h)分别为66076μg·h/L与70334μg·h/L,AUC(0-∞)分别为68153μg·h/L与72362μg·h/L,峰浓度(peak concentration,Cmax)分别为6631.5μg/L与7033.9μg/L,半衰期(T1/2,half-time)分别为15.39±4.61h与16.06±5.56h,达峰时间(peak time,Tmax)分别为1.3±0.9h与1.4±0.7h。试验用罗红霉素胶囊试验制剂的相对生物利用度为94.9%±22.4%,试验制剂AUC(0～72h)和Cmax的90%置信区间为参比制剂相应参数的86.2%～98.9%和88.3%～101.2%。本法简便,灵敏准确。试验用罗红霉素胶囊与参比制剂生物等效。
To establish a human plasma roxithromycin HPLC-MS method to study the pharmacokinetics and bioavailability of two roxithromycin capsules in healthy volunteers. Thirty-six healthy young male volunteers were randomly divided into two groups: crossover self-control trial and double crossover study. A single oral dose of 150 mg roxithromycin reference formulation or test preparation was used to determine the concentration of roxithromycin in plasma by HPLC-MS. The results showed that the average area under the curve (AUC) of AUC (0 ~ 72h) of the roxithromycin capsules after treatment with DAS2.0 pharmacokinetic program were 66076μg · h / L and 70334μg · AUC (0-∞) were 68153μg · h / L and 72362μg · h / L respectively, and the peak concentrations (Cmax) were 6631.5μg / L and 7033.9μg / L, , half-time were 15.39 ± 4.61h and 16.06 ± 5.56h respectively, peak time (Tmax) were 1.3 ± 0.9h and 1.4 ± 0.7h, respectively. The relative bioavailability of test roxithromycin capsules was 94.9% ± 22.4%. The 90% confidence intervals of AUC (0 ~ 72h) and Cmax of test preparations were 86.2% ~ 98.9% and 88.3% of the corresponding parameters of reference preparations % ~ 101.2%. This method is simple, sensitive and accurate. The roxithromycin capsules were bioequivalent to the reference formulation.