国产头孢氨苄片与国外同品种的人体生物等效性研究

Bioequivalence Evaluation of Domestic Cefalexin Tablets Compared with the Same US Product in Chinese Healthy Volunteers

目的 考察两种（国产与国外同品种）头孢氨苄片的人体生物利用度，评价两制荆在健康人体的生物等效性。方法 将20例健康志愿者随机平均分为两组，交叉口服单剂量试验制剂（国产）和参比制剂头孢氨苄片（美国梯瓦制药生产）500mg，停药清洗期为1周。采用高效液相色谱法测定血浆头孢氨苄浓度。结果 单剂量口服试验制剂与参比制剂头孢氨苄片后，两药的主要药动学参数分别为tmax：（0．95±0．40）和（0．99±0．33）h；cmax：（19．53±5．20）和（19．03±4．39）μg·mL^-1；t1／2：（1．03±0．17）和（1．00±0．20）h；AUC0→6h：（33．26±6．60）和（33．39±6．39）μg·h·mL^-1；AUC0→∞：（34．05±6．83）和（34．21±6．86）μg·h·mL^-1。试验制剂与参比制剂比较，人体相对生物利用度为（99．8±8．0）％。试验制剂的AUC0→6h和AUC0→90％可信区间分别为96．4％-102．6％和96．5％-102．6％；Cmax的90％可信区间为94．6％-109．4％。两制剂tmax差异无显著性（P〉0．05）。结论 单剂量口服试验或参比制剂后，两制剂的主要药代动力学参数Cmax，AUC0→6h、AUC0→∞和tmax均差异无显著性，国产头孢氨苄片与美国梯瓦制药生产的头孢氨苄片具有生物等效性。

Objective To study the relative bioavailability in Chinese healthy volunteers of the test cefalexin tablets （QINGYUAN HUANENG PHARMACEUTICAL CO. , LTD. CHINA ） compared with the reference cefalexin tablets （Teva Pharmaceutical Industries Ltd） and to evaluate the bioequivalence of these two products. Methods The bioequivalence of two products of cefalexin tablet 500 mg was demonstrated in 20 Chinese healthy male volunteers after a single oral administration in a randomized, two-treatment, two-period crossover design with a 1 week washout period. The HPLC method was applied for the measurement of cefalexin in plasma samples. Results After oral administration, the major pharmacokinetic parameters of two products were calculated from the plasma cefalexin concentration -time profile. For test and reference products , the time to reach maximum concentration （ t max ） was （0.95 ± 0.40 ） and （0.99 ±0. 33 ） h, the peak concentration （ Cmax ） was （ 19.53 ± 5.20） and （19.03 ±4.39） g ·mL^-1, the half- life （t1/2） was （1.03 ±0.17） and （1.00 ±0.20） h, the area under the curve to the last measurable concentration （AUC0-6h） was （33.26 ± 6.60）and （33.39±6.39） μg ·h ·mL^-1, the area under the curve to infinity （AUC0→∞） was （34.05±6.83） and （34.21 ±6. 86）μg·h· mL^-1 ,respectively. The result from comparison of AUC0-6 h of two products indicated the relative bioavailability of test product was （99.8±8.0） % . The 90% confidence interval （90% CI）ofAUC0-6h and AUC0→∞ of test product were 96. 4 %-102.6 % and 96.5%- 102.6% , 90% CI of Cmax was 94.6%- 109.4%. The non-parametric test of Wilcoxon signed rank test on tmax shown no significant difference （ P 〉 0.05 ） between the cefalexin test and reference tablets. Condnsion Based on these statistical inference and the bioequivalence criteria , it is concluded that the domestic cefalexin tablet and TEVA cefalexin tablet are bioequivalent, and that the two formulations should be considered equally effective and safe in medical practice.