国产与进口头孢地尼颗粒在健康人体的生物等效性研究  

Bioequivalence of domestic and imported Cefdinir Granule in healthy volunteers

作　　者：赵红娜[1] 刘曼[1] 王晓琳[1] 马婧怡[1] 张丽娜[1] 刘敏[1] 张丹[1] 佟阳[1] 刘会臣[1] 

机构地区：[1]航天中心医院临床药理室,北京100049

出　　处：《现代药物与临床》2015年第10期1192-1197,共6页Drugs & Clinic

摘　　要：目的建立测定人血浆中头孢地尼的液相色谱-串联质谱（LC-MS/MS）方法,并用于评价头孢地尼颗粒在人体的生物等效性。方法 24名健康男性受试者随机交叉单剂量口服头孢地尼颗粒受试制剂和参比制剂100 mg,采用LC-MS/MS法测定人血浆样本中头孢地尼,Win Nonlin 6.3软件计算其药动学参数,并评价两种制剂的生物等效性。结果血浆中头孢地尼的线性范围为10.0~2 000 ng/m L（r=0.999 7）,定量下限为10.0 ng/m L;批内、批间精密度（RSD）均小于6.0%,准确度（RE）在±4.0%以内;随着放置时间的延长,血浆中头孢地尼在室温条件下降解程度增加。受试制剂和参比制剂的AUC0-t分别为（6 238.22±1 993.74）、（6 331.35±1 850.42）ng·h/m L,AUC0-∞分别为（6 343.68±2 070.73）、（6 429.76±1 901.33）ng·h/m L,Cmax分别为（1 290±391）、（1 330±384）ng/m L,tmax分别为2.50（2.00~4.50）、2.50（2.00~3.50）h,t1/2分别为（1.61±0.17）、（1.61±0.17）h。AUC0-t、AUC0-∞和Cmax的几何平均数比值（GMR）分别为97.88%、97.95%、96.75%,其90%置信区间分别为91.75%~104.42%、91.76%~104.56%、90.43%~103.52%。结论该方法快速、灵敏、准确、专属性强、重现性好,适用于人血浆头孢地尼的测定。头孢地尼颗粒受试制剂和参比制剂具有生物等效性。Objective To develop a liquid chromatography-tandem mass spectrometry（LC-MS/MS） method for the determination of cefdinir in human plasma and evaluate the bioequivalence of its two granules. Methods A single oral dose of 100 mg cefdinir test and reference granules were given to 24 healthy male volunteers in a randomized, two-way crossway study. The concentrations of cefdinir in plasma were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by Win Nonlin 6.3 Software, and the bioequivalence of the two preparations was evaluated. Results The linear range for determining cefdinir in plasma samples was 10.0 — 2000 ng/m L（r = 0.999 7）, with the lower limit of quantification（LLOQ） of 10.0 ng/m L. The intra- and inter-batch relative standard deviation（RSD） was lower than 6.0%, and relative error（RE） was within ± 4.0%. Degradation degree of cefdinir in human plasma was increased under the room temperature storage with the extension of storage time. The main pharmacokinetic parameters of test and reference preparations were as follows： AUC0-t were（6238.22 ± 1993.74） and（6331.35 ± 1850.42） ng·h/m L; AUC0-∞ were（6 343.68 ± 2070.73） and（6429.76 ± 1901.33） ng·h/m L; Cmax were（1290 ± 391） and（1330 ± 384） ng/m L; tmax were 2.50（2.00 — 4.50） h and 2.50（2.00 — 3.50） h; t1/2 were（1.61 ± 0.17） and（1.61 ± 0.17） h, respectively. The geometric mean ratios（GMRs） for AUC0-t, AUC0-∞, and Cmax were 97.88%（90% CI, 91.75% — 104.42%）, 97.95%（90% CI, 91.76% — 104.56%） and 96.75%（90% CI, 90.43% — 103.52%）, respectively. Conclusion The established method is rapid, sensitive, accurate, selective, reliable, and sufficient for the determination of cefdinir in human plasma, andthe two preparations are bioequivalent.

关 键 词：头孢地尼颗粒 头孢地尼 LC-MS/MS 生物等效性 

分 类 号：R969.1[医药卫生—药理学] R978.1[医药卫生—药学]