头孢克洛干混悬剂药动学及生物等效性研究.docVIP

头孢克洛干混悬剂的药动学及生物等效性研究 [摘要] 摘　要：目的　研究头孢克洛干混悬剂的人体生物利用度和生物等效性。方法 采用随机交叉试验设计，20名健康男性志愿者单剂量口服两种头孢克洛干混悬剂250 mg，用液相色谱-串联质谱法测定血浆中头孢克洛的浓度，将20名受试者的经时血药浓度录入DAS（ver 1.0）程序，进行统计分析。结果 单剂量口服试验与参比制剂后头孢克洛的Cmax分别为（9.00±1.68）和（9.59±1.61）(g·mL-1，Tmax分别为（0.37±0.12）和（0.35±0.05）h，t1/2分别（0.88±0.16）和（0.87±0.11）h，AUC0-5 h分别为（7.91±1.00）和（7.91±1.10）(g·h·mL-1，AUC0-∞分别为（7.98±1.02）和（7.98±1.11）(g·h·mL-1，max进行非参数秩和检验，Cmax、AUC0-5 h、AUC0-∞经对数转换后做方差分析，并经双向单侧t检验；两制剂的Tmax、Cmax、AUC0-5 h、AUC0-∞均无显著性差异，受试制剂的AUC0-5 h、AUC0-∞的90 %可信限落在参比制剂的80 %～125 %范围内；Cmax的90%可信限落在参比制剂的70 %～143 %范围内。试验制剂的相对生物利用度为（100.7±12.5）%。结论 试验制剂与参比制剂具有生物等效性。 [关键词] 头孢克洛；干混悬剂；相对生物利用度；生物等效性；药动学；高效液相色谱-串联质谱法 Pharmacokinetic properties and bioequivalence of cefaclor for suspension after single dose administration in healthy volunteers ABSTRACT：AIM To study the bioequivalence and relative bioavailability of two cefaclor for suspensions. METHODS A single oral adminstration of 250 mg test and reference suspensions were given to 20 healthy male volunteers according to a randomized crossover design. The concentrations of cefaclor in plasma were determined by a HPLC/MS/MS method. The pharmacokinetic parameters were calculated and the bioequivalence were compared by DAS (ver 1.0) program. RESULTS The pharmacokinetic parameters of test and reference preparations were as follows: Cmax were (9.00±1.68) and (9.59±1.61) (g·mL-1，Tmax were (0.37±0.12) and (0.35±0.05) h，t1/2 were (0.88±0.16) and (0.87±0.11) h，AUC0-5 h were (7.91±1.00) and (7.91±1.10) (g·h·mL-1，AUC0-∞were (7.98±1.02) and (7.98±1.11), respectively. There were no significant differences (P0.05) in Tmax, Cmax, AUC0-5h, AUC0-∞and t1/2 between the two preparations. The relative bioavailability of test suspensions was (100.7±12.5) %. CONCLUSION The test and reference preparations were bioequivalence. KEY WORDS: cefaclor, suspension, relative bioavailability, bioequivalence, pharmacokinetics, HPLC/MS/MS Cefaclor (Cef), 3-chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid, is a semisynt