摘要
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。
Abstract This is a study of assessing the comparative bioavailability of roxithromycin produced by two companies in 36 healthy volunteers. On the basis of informed consent, 36 healthy male volunteers received each medicine at the roxithromycin dose of 150mg in a cross-over study. There was a 1-week washout period among the doses. Plasma concentrations of roxithromycin were monitored by an LC-MS/MS for over a period of 72 hours after administration. In this study, roxithromycin was generally well tolerated. After an oral administration of roxithromycin capsule, the pharmacokinetic parameters of roxithromycin, such as AUC（0-72 h） （66 076 μg·L · h^-1 and 70 334 μg·L · h^-1 for test and reference capsule, respectively） and AUC（0-∞） （68 153 μg·L · h^-1 and 72 362 μg·L · h^-1 ） were significantly similar. For test and reference capsule, the values of Cmax were 6 631.5 μg·L · h^-1 and 7 033.9μg·L-1 respectively,of T1/2 were 15.39±4.61h and 16.06±5.56 h,and of Tmax were 1.3±0. 9 h and 1.4±0.7 h respectively. The relative bioavailability F was 94.9%±22.4% of tested formulation. The values of 90% confidence interval around the ratios （test/reference） （obtained by analysis of variance, ANOVA） were 88. 3%-101.2% for C 86.2%- 98.9% for AUC（0-72 h）, being within the predefined acceptable range for the conclusion of bioequivalence. The results of statistical analysis suggest that the two formulations be bioequivalent.
出处
《生物医学工程学杂志》
EI
CAS
CSCD
北大核心
2009年第6期1315-1319,共5页
Journal of Biomedical Engineering
