阿莫西林克拉维酸钾的质量分析及人体生物等效性、生物利用度研究

目的：评价阿莫西林克拉维酸钾的质量，并探讨其人体生物等效性、生物利用度。方法：24例健康志愿者随机交叉口服阿莫西林克拉维酸钾片（参比制剂）或阿莫西林克拉维酸钾分散片（受试制剂）625 mg后，采用液质联用仪测定血浆中阿莫西林、克拉维酸钾的血药浓度，并计算药动学参数及评价生物等效性。结果：国产制剂不同批次的样品含量差异较小，生产质量稳定；但单个杂质及总杂质均高于进口制剂。参比制剂中阿莫西林C_max（6.836±2.453）μg·mL^-1、t_max（1.8±0.8） h、t_1/2（1.6±0.2） h、AUC_0-∞（23.2±4.2）μg·h·mL^-1；克拉维酸钾C_max（3.644±0.406）μg·mL^-1、t_max（1.5±0.4） h、t_1/2（1.5±0.3） h、AUC_0-∞（24.1±5.6）μg·h·mL^-1。受试制剂中阿莫西林C_max（6.717±2.463）μg·mL^-1、t_max（1.5±0.5） h、t_1/2（1.4±0.3） h、AUC_0-∞（23.5±5.3）μg·h·mL^-1；克拉维酸钾C_max（3.597±0.399）μg·mL^-1、t_max（1.6±0.3） h、t_1/2（1.5±0.2） h、AUC_0-∞（24.5±4.8）μg·h·mL^-1。经计算可知受试制剂的单次给药后阿莫西林的相对生物利用度为96.6%，克拉维酸钾的相对生物利用度为97.3%，受试制剂与参比制剂生物等效。结论：阿莫西林克拉维酸钾分散片含量及有关物质符合药典标准，且与阿莫西林克拉维酸钾片人体生物等效性。

Study on the quality of amoxicillin and clavulanate potassium and its bioequivalence and bioavailability

OBJECTIVE To evaluate the quality of Amoxicillin and Clavulanate Potassium and to investigate its bioequivalence and bioavailability.METHODS 24 healthy volunteers were randomly assigned to oral administration of amoxicillin clavulanate potassium tablets (reference preparation) or amoxicillin clavulanate potassium dispersible tablets (test preparation)625 mg.The plasma concentration of amoxicillin and clavulanate potassium were determined by liquid chromatography combined with mass spectrum and the pharmacokinetic parameters and bioequivalence were calculated and evaluated.RESULTS The content of samples of different batches of domestic preparations varied little and the production quality was stable,but the single impurities and overall impurities were higher than those of imported preparations.The C_max,t_max,t_1/2,AUC_0-∞ of amoxicillin in reference preparation were (6.836±2.453)μg·mL^-1,(1.8±0.8) h,(1.6±0.2) h,(23.2±4.2)μg·h·mL^-1.The C_max,t_max,t_1/2,AUC_0-∞ of clavulanate potassium in reference preparation were (3.644±0.406)μg·mL^-1,(1.5±0.4) h,(1.5±0.3) h,(24.1±5.6)μg·h·mL^-1.The C_max,t_max,t_1/2,AUC_0-∞ of amoxicillin in test preparation were (6.717±2.463)μg·mL^-1,(1.5±0.5) h,(1.4±0.3) h,(23.5±5.3)μg·h·mL^-1.The C_max,t_max,t_1/2,AUC_0-∞ of clavulanate potassium in test preparation were (3.597±0.399)μg·mL^-1,(1.6±0.3) h,(1.5±0.2) h,(24.5±4.8)μg·h·mL^-1.The bioavailability of amoxicillin in test preparation was 96.6%,while the bioavailability of clavulanate potassium in test preparation was 97.3% after single dose administration of the test formulation..The test formulation was bioequivalent to the reference formulation.CONCLUSION Amoxicillin and clavulanate potassium dispersible tablet content and related substances meet the pharmacopoeia standards,and bioequivalent to amoxicillin and clavulanate potassium tablets.