阿莫西林·克拉维酸钾片在健康志愿者体内的相对生物等效性

Relative bioequivalence and pharmacokinetics of amoxicillin·clavulanic acid in healthy volunteers

目的 比较两种不同工艺生产的阿莫西林·克拉维酸钾片在健康志愿者体内的药代动力学及相对生物等效性 ,确保临床用药质量 .方法 健康志愿受试者 18例 ,男性 ,采用标准二阶段交叉设计自身对照试验法 ,用 RP- HPL C法测定血浆中阿莫西林和克拉维酸的经时浓度 ,以双单侧 t检验统计法比较两种不同工艺生产的阿莫西林·克拉维酸钾片之间的差异 .结果 两种阿莫西林·克拉维酸钾片在健康志愿者体内的药时曲线均符合一级吸收的单室开放模型 ,主要的药代动力学参数阿莫西林 :tmax分别为 (71.7± 9.7)和 (6 9.2±9.1) min,ρmax,AUC( 0～ 3 6 0 min) 分别为 :(8.8± 1.5 )和 (8.0±1.3) mg· L- 1 ;(140 6± 30 8)和 (12 39± 2 5 0 ) (mg· m in- 1 ·L- 1 ) ,Cla:tmax分别为 (6 8.3± 7.7)和 (6 7.5± 7.7) m in,ρmax,AU C( 0～ 3 6 0 min) 分别为 :(6 .2± 0 .8)和 (5 .9± 0 .7) mg· L- 1 ;(10 33± 176 )和 (96 2± 136 ) (mg· min- 1· L- 1 ) ,药动学参数间均无统计学差异 (P>0 .0 5 ) ,相对生物利用度阿莫西林 F为 115 % ;克拉维酸 F为 10 8% .结论 两种阿莫西林·克拉维酸钾片在健康志愿者体内具有相同的生物效应 。

AIM To compare the pharmacokinetic parameters and relative bioavailability of amoxicillin potassium clavulanic tablets produced by different technique and to ensure quality of the medicine. METHODS An open, randomized, two period crossover study with a two week washout interval was conducted in 18 healthy volunteers. Concentrations of amoxicillin and clavulanic acid in plasma were assayed by HPLC method. The main pharmacokinetics parameters (AUC, ρ max and t max ) were analyzed by two one sided t test. RESULTS The concentration time curve after medication conformed to a 1 compartment open model with a first order absorption. The AUC (0~360 min) , ρ max and t max of amoxicillin were (1406±308) and (1239±250) (mg·min -1 ·L -1 ), (8.8±1.5) and (8.0±1.3) mg·L -1 , (71.7±9.7) and (69.2±9.1) min respectively. The AUC (0~360 min) , ρ max and t max of Clavulanic acid were (1033±176) and (962±136) (mg·min -1 ·L -1 ), (6.2±0.8) and (5.9±0.7) mg·L -1 , (68.3±7.7) and (67.5±7.7) min respectively. CONCLUSION The relative bioavailability of amoxicillin and clavulanic acid was 115% and 108% respectively. Two tables are bioequivalent.