头孢克洛分散片健康人体药动学与生物等效性评价

Pharmacokinetics and Bioequivalence of Cefaclor Dispersible Tablets

目的建立人血浆头孢克洛浓度测定方法,进行头孢克洛分散片人体药动学研究与生物等效性评价。方法24例健康受试者随机交叉、单剂量口服试验和参比头孢克洛分散片500 mg,采用高效液相色谱法测定血浆头孢克洛浓度,计算其人体药动学参数,并进行生物等效性评价。结果头孢克洛线性范围0.150 4 ～24.060 0 mg·L^-1（权重＝1/CC,r＝0.999 0）,最低定量浓度0.150 4 mg·L^-1,低、中、高浓度平均绝对回收率分别为81.82%,85.31%,86.58%,平均相对回收率分别为94.20%,98.43%,101.40%。试验和参比制剂的主要药动学参数：Cmax分别为（12.882±2.494）和（12.578±3.143） mg·L^-1;tmax分别为（0.615±0.165）和（0.663±0.345）h ;t1/2分别为（0.824±0.164）和（0.808±0.175） h ;AUC0→t分别为（16.039±2.666）和（15.367±2.776） mg·h·L^-1;AUC0→∞分别为（16.301±2.729）和（15.646±2.874） mg·h·L^-1。以AUC0→t计算受试制剂的相对生物利用度为（105.6±13.8）%。结论建立的高效液相色谱法专属性强,准确,灵敏度适宜;经方差分析及双单侧t检验结果显示,试验制剂和参比制剂在人体内生物等效。

ObjectiveTo set up the way for determining cefaclor plasma levels and study pharmacokinetics and bioequivalence of those in Chinese healthy volunteers. MethodsA single oral dose of 500 mg test or reference of cefaclor dispersible tablets was given to each volunteer according to an open randomized crossover design. The concentrations of cefaclor in plasma were determined by HPLC method. The pharmacokinetic parameters were calculated and bioequivalence was evaluated. ResultsA linear calibration curve for assay of cefaclor in plasma was obtained in the range of 0.150 4～24.060 0 mg·L-1 with the limit of quantitation of 0.150 4 mg·L-1 and the absolute recoveries was at least 80%. The main pharmacokinetic parameters of test and reference of cefaclor dispersible tablets were as follows： Cmax（12.882±2.494）and（12.578±3.143） mg·L-1;tmax （0.615±0.165）and（0.663±0.345） h; t1/2（0.824±0.164）and（0.808±0.175） h;AUC0→t（16.039±2.666）and（15.367±2.776） mg·h·L-1;AUC0→∞（16.301±2.729）and（15.646±2.874） mg·h·L-1. The relative bioavailability of the test tablets was （105.6±13.8）%. ConclusionThe established HPLC technique is specific, accurate and sensitive. The result shows that the two formulations are bioequivalent in human by ANOVA, and both bilateral and monolateral t test.