阿莫西林克拉维酸钾片的人体生物等效性研究

 目的 对国产和进口阿莫西林克拉维酸钾(7:1)片剂进行生物等效性评价。方法 18名健康志愿者按标准的2×2交叉试验方案设计,禁食12 h后空腹口服进口(参比)制剂或国产(受试)制剂各800 mg(以阿莫西林含量计算),并采集8 h内动态血标本;采用RP-HPLC荧光检测法检测血清中药物浓度,并计算相关药动学参数,判定两制剂是否生物等效。结果 参比制剂阿莫西林克拉维酸钾咀嚼片及受试制剂阿莫西林克拉维酸钾片的主要药动学数据,克拉维酸的t_max分别为(1.11±0.46)和(1.28±0.43)h,c_max分别为(2.73±1.04)和(2.66±1.11)mg·L^-1,AUC_0-5分别为(6.09±1.96)和(5.93±1.89)mg·h·L^-1,t_1/2ke分剐为(1.45±0.35)和(1.59±0.54)h,Ke分别为(0.50±0.11)和(0.47±0.11)h^-1;阿莫西林的t_max分别为(2.11±0.53)和(2.19±0.73)h,c_max分别为(21.55±5.75)和(20.26±3.84)mg·L^-1,AUC_0-t分别为(79.21±12.72)和(77.37±9.14)mg·h·L_-1,t_1/2ke分别为(1.87±0.36)和(2.03±0.43)h,Ke分别为(0.38±0.06)和(0.36±0.08)h^-1两种制剂的克拉维酸及阿莫西林主要药动学参数c_max,AUC_0-t经对数转换后进行方差分析及双单侧t检验,并计算90％置信区间,表明两种制剂生物等效,克拉维酸及阿莫西林的相对生物利用度分别为(98.21±13.99)％和(99.25±14.17)%. 结论 两种制剂生物等效。

Study on bioequivalence of amoxycillin-potassium clavulanate tablets

OBJECTIVE To study the bioequivalence of domestic and imported amoxycillin-potassium clavulanate tablets in healthy volunteers. METHODS 800 mg( calculated as amoxycillin) imported or domestic tablets were given to 18 healthy male volunteers in a randomized two-way crossover design. The concentrations of clavulanic acid and amoxycillin were determined by RP-HPLC with fluorescence detection . RESULTS The pharmacokinetic parameters of clavulanic acid of imported and domestic tablets were as following:t_max(1.11±0.46) and (1.28±1.96)h, c_max(2.73±1.04) and (2.66±1.11)mg·L^-1 ,AUC_O-t(6.09±1.96) and (5.93±1.89)mg·L^-1,t_1/2ke(1.45±0.35) and (1.59±0.54)h and Ke(0.50±0.11) and (0.47±0.11)h respectively.The pharmacokinetic parameters of amoxycillin were as following: t_max(2.11±0.53) and(2.19±0.73)h,c_max(21.55±5.75) and (20.26±3.84)mg·L^-1 ,AUC_0-t,(79.21±12.72) and (77.37±9.14)mg·h·L^-1,t_1/2ke (1.87±0.36) and (2.03±0.43)h and Ke(0.38±0.06) and (0.36±0.08)h^-1 respectively.The mean relative bioavailability of domestic tablets vs imported product were(98.21±13.99)% for clavulanic acid and (99.25±14.17)% for amoxycillin.CONCLUSION The two formulations were bioequivalent.