地红霉素肠溶微丸颗粒生物等效性研究  

Bioequivalence of Dirithromycin Enteric-coated Micropill Granules in Healthy Volunteers

作　　者：王贵发[1] 丁玉峰[2] 赵红英[1] 李功华[1] 

机构地区：[1]浙江省人民医院药学部,杭州310014 [2]华中科技大学同济医学院附属同济医院药学部,武汉430030

出　　处：《医药导报》2012年第10期1297-1300,共4页Herald of Medicine

摘　　要：目的建立测定人血浆中红霉素胺浓度的液相色谱-质谱联用(LC-MS)方法,研究地红霉素肠溶微丸颗粒在健康志愿者中的生物利用度,评价试验制剂和对照制剂的生物等效性。方法采用两制剂双周期自身对照交叉试验设计,20名健康志愿者,单剂量口服地红霉素试验制剂和参比制剂各500 mg,用LC-MS法测定血浆代谢物红霉素胺的浓度。用DAS软件处理血药浓度数据和计算参数,并进行统计学分析。药物浓度-时间曲线下面积(AUC)及峰浓度(Cmax)经对数转换后作多因数方差分析和双单侧t检验并计算90%可信区间;达峰时间(tmax)进行非参数检验,对两种制剂作出生物等效性评价。结果建立血浆红霉素胺浓度的HPLC-MS测定法。红霉素胺的浓度与吸收峰面积比值在浓度5～1 000 ng.mL-1范围内呈线性关系,线性回归方程为A=68.87C+1.47(r=0.999 7),最低检测浓度为5 ng.mL-1。低、中、高浓度的方法回收率为98.32%,99.16%,97.87%,平均提取回收率为72.42%,71.63%,73.38%,日内、日间RSD均小于9%。单剂量口服500 mg的地红霉素试验制剂和参比制剂的主要药动学参数AUC0→96分别为(3 537.39±576.32)和(3 065.47±558.63)ng.mL-1.h,AUC0→∞分别为(4 059.27±737.25)和(3 831.76±687.51)ng.mL-1.h;Cmax分别为(415.84±81.24)和(420.36±63.21)ng.mL-1;tmax为(3.25±0.28)和(3.47±0.35)h。受试制剂的相对生物利用度为(105.72±17.83)%。结论 LC-MS测定法适用于测定人血浆中红霉素胺的浓度。统计分析结果表明,两种制剂的主要药动学参数之间无明显差异,两种制剂具有生物等效性。Objective To study relative bioavailability and evaluate bioequivalence following oraladministration of reference capsules and test Enteric-coated micro-pill granules of dirithromycin in healthy volunteers.Methods A single oral dose of 500 mg test or reference preparations of dirithromycin was given to 20 healthy volunteers in a randomized crossover study.The plasma concentrations of erythromycylamine were determined by HPLC-MS.The pharmacokinetic parameters were calculated with DAS2.0.The bioavailability and bioequivalence were evaluated.Results The detection limit of erythromycylamine in plasma was 5 ng·mL^-1and a good linearity relationship was obtained over the range of 5-1 000 ng·mL^-1,the linearity relationship was A=68.87C ＋1.47（r=0.999 7）.The relative standard deviation of within-day and between-day was less than 9%.The pharmacokinetic parameters of test and reference preparations after a single oral dose were as following： AUC0→96 were（3 537.39±576.32） and（3 065.47±558.63） ng·mL^-1·h;AUC0→∞ were（4 059.27±737.25） and（3 831.76±687.51） ng·mL^-1·h;Cmax were（415.84±81.24） and（420.36±63.21）ng·mL^-1;tmax were（3.25±0.28） and（3.47±0.35）h.the relative bioavailability of tested granules was（105.72±17.83）%.Conclusion The LC-MS method was suitable for assaying erythromycylamine in plasma.Statistic analysis showed no significant differences between the two preparations of dirithromycin,and the bioequivalence of two preparations was equal.

关 键 词：地红霉素 红霉素胺 生物等效性 

分 类 号：R978.16[医药卫生—药品] R969.1[医药卫生—药学]