克拉维酸钾羟氨苄青霉素分散片的人体生物利用度

Relative bioavailability of potassium clavulanate and amoxicillin dispersible tablet

目的 :研究克拉维酸钾羟氨苄青霉素分散片在健康志愿者体内的相对生物利用度。方法 :交叉口服单剂量克拉维酸钾羟氨苄青霉素分散片 (受试制剂 )和克拉维酸钾羟氨苄青霉素片 (参比制剂 ) ,用反相高效液相色谱法测定人血清中克拉维酸钾和羟氨苄青霉素的浓度。使用NDST程序对各药物动力学参数进行方差分析和双单侧t检验。结果 :受试制剂的克拉维酸钾和羟氨苄青霉素的AUC0→ 8,cmax,tmax,T1/ 2 分别为 (3 18± 1 5 8)h·μg·mL-1,(1 5 0± 0 90 ) μg·mL-1,(1 33± 0 5 9)h ,(1 0 2±0 34 )h和 (13 6 6± 1 16 )h·μg·mL-1,(6 5 5± 1 46 ) μg·mL-1,(1 0 3± 0 42 )h ,(1 15± 0 32 )h ;参比制剂的克拉维酸钾和羟氨苄青霉素的AUC0→ 8,cmax,tmax,T1/ 2 分别为 (2 76± 0 84)h·μg·mL-1,(1 32± 0 47)h·μg·mL-1,(1 5 3± 0 71)h ,(1 2 8± 0 5 1)h和(11 0 3± 1 5 3)h·μg·mL-1,(5 0 8± 1 2 8) μg·mL-1,(1 0 5± 0 2 6 )h ,(1 0 4± 0 47)h。受试制剂中克拉维酸钾和羟氨苄青霉素的相对生物利用度分别为 112 80 %和 12 6 14%。克拉维酸钾的AUC0→ 8和cmax在 2药间比较无显著差异 ,而羟氨苄青霉素的AUC0→ 8和cmax具显著差异 ,受试制剂中较高。结论

AIM: To study the relative bioavailability of potassium clavulanate and amoxicillin dispersible tablet in 10 healthy male Chinese volunteers. METHODS: According to the crossover design, each volunteer was given a single oral dose of 625 mg test tablet and reference tablet. The serum concentrations of potassium clavulanate and amoxicillin were determined by high performance liquid chromatography(HPLC). Pharmacokinetic paramters were calculated. The analysis of variance and two one side t test were used to evaluate the variance between 2 groups. RESULTS: For a single dose test tablets, the AUC 0→t , c max , t max , T 1/2 of potassium clavulanate and amoxicillin were (3 18±1 58) h·μg·mL -1 ,(1 50±0 90) μg·mL -1 ,(1 33±0 59) h,(1 02±0 34) h and (13 66±1 16) h·μg·mL -1 ,(6 55±1 46) μg·mL -1 ,(1 03±0 42) h,(1 15±0 32) h, respectively. The reference tablets were (2.76±0 84) h·μg·mL -1 , (1 32±0 47) μg·mL -1 ,(1 53±0 71) h,(1 28±0 51) h and (11 03±1 53) h·μg·mL -1 ,(5 08±1 28) μg·mL -1 ,(1 05±0 26) h,(1 04±0 47) h, respectively. The relative bioavailability of potassium clavulanate and amoxicillin of test tablets were 112 80% and 126 14%, respectively. All pharmacokinetic parameters of potassium clavulanate had no significant difference between 2 preparations, but the AUC 0→8 and c max of amoxicillin of test tablets were significantly higher than that of reference tablets. CONCLUSION: The 2 preparations are not bioequivalent. The test tablets have higher bioavailability than that of the reference tablets.