阿莫西林与克拉维酸按7∶1配比的药代动力学和生物等效性研究

Pharmacokinetics and bioequivalence study of amoxycillin and clavulanic acid (7∶ 1)— —a new combination in healthy male volunteers

目的了解阿莫西林和克拉维酸在中国健康人体中的药代动力学并比较两种不同产地阿莫西林/克拉维酸低配比(7∶1)制剂的生物等效性。方法20名男性健康受试者采用随机交叉给药方案,分别口服1000mg阿莫西林/克拉维酸片(内含阿莫西林875mg,克拉维酸125mg),用HPLC法分别测定血清中阿莫西林和克拉维酸的浓度,按照最佳拟合的方法求算两种药物的药代动力学参数,并计算两种制剂的相对生物利用度。结果两种制剂的血药浓度—时间曲线符合一房室模型。两种制剂—对照药和试验药的阿莫西林、克拉维酸的达峰时间Tmax分别为(1.57±0.61)、(1.31±0.31)h和(1.75±0.53)、(1.33±0.33)h,Cmax分别为(11.05±2.16)、(2.10±0.54)mg/L和(11.56±7.71)、(2.00±0.51)mg/L。t1/2分别为(1.30±0.37)、(0.98±0.20)h和(1.29±0.25)、(0.91±0.17)h,AUC0-∞分别为(34.47±4.32)、(4.95±1.03)mg·h/L和(35.90±6.25)、(5.00±1.04)mg·h/L。试验药物的阿莫西林相对生物利用度为(104.4±16.5)%,克拉维酸为(96.7±11.7)%,AUC经统计学处理证实两种制剂生物等效。

Pharmacokinetics study of amoxycillin and clavulanic acid in 7∶ 1 ratio were performed in 20 healthy subjects in a randomized and cross over way,and the bioequivalene were compared for the two preparations tested.After each subject was orally given 1000mg of amoxycillin (875mg) and clavulanic acid (125mg),serum samples at different time were taken and the concentrations of amoxycillin and clavulanic acid were measured by using validated HPLC methods.The profiles of the time concentration curves of amoxycillin and clavulanic acid were best fitted to a one compartment model,and the pharmacokinetic parameters were obtained as following:for reference drugs Tmax were:(1.75± 0.53)h (amoxycillin),(1.33± 0.33)h (clavulanic acid);Cmax were (11.56± 7.71)mg/L (amoxycillin), (2.00± 0.51)mg/L (clavulanic acid);t1/2 were (1.29± 0.25h) (amoxycillin),(0.91± 0.17)h (clavulanic acid);AUC0- t were (35.90± 6.25)mg· h/L (amoxycillin),(4.74± 1.03)mg· h/L (clavulanic acid);AUC0- ∞ were (36.79± 6.51) (amoxycillin)mg· h/L,(4.79± 1.03)mg· h/L (clavulanic acid);Relative bioavailability of test drug was (104.4± 16.5)% for amoxycillin,(96.5± 11.7)% for clavulanic acid,and the two preparations were proved to be bioequivalent.