头孢地尼干混悬剂的生物等效性与人体药动学研究

Pharmacokinetics and Bioequivalence Study of Cefdinir Suspension in Healthy Volunteers

目的建立液相色谱-串联质谱(LC-MS/MS)法测定受试者口服头孢地尼受试制剂(干混悬剂)和参比制剂(胶囊)后的血药浓度,估算两制剂的药动学参数并评价生物等效性。方法采用随机、开放、双周期交叉试验设计,24例中国男性健康受试者单剂量口服受试制剂和参比制剂100 mg后,血浆样品经甲醇直接沉淀蛋白后进行LC-MS/MS分析,利用DAS2.1.1软件计算药动学参数,并进行生物等效性评价。结果受试制剂和参比制剂血浆中头孢地尼的峰浓度(Cmax)分别为(1 008±259)和(997.5±277.6)μg.L-1,达峰时间(tmax)分别为(2.7±0.9)和(3.6±0.6)h,t1/2分别为(1.7±0.2)和(1.7±0.3)h,AUC0-12 h分别为(5 279±1 204)和(5 357±1 291)μg.L-1.h,相对生物利用度为(100.3±16.2)%。结论该试验建立血浆头孢地尼浓度测定方法准确、灵敏、简便,统计结果表明受试制剂和参比制剂生物等效。

Objective An LC-MS/MS method was developed for the determination of cefdinir in human plasma and evaluating pharmacokinetics and bioequivalenee of cefdinir in healthy volunteers. Methods This randomized sequence, open- label, two-period crossover study was performed in 24 fasting healthy Chinese males. They were randomly assigned to receive 100 mg of either the test or reference formulation orally. Plasma concentrations were determined by LC-MS/MS after protein precipitation with methanol. The pharmacokinetie parameters were calculated by DAS2. 1. 1. Results The main pharmacokinetic parameters of cefdinir in test and reference preparations were as follows： the values of Cmax were （1 008±259 ） and （997.5±277.6） μg · L ^-1· max were （2.7±0.9） and （3.6±0.6） h,t1/2 were （1.7±0.2） and （1.7±0.3） h,AUC0.12h were （5 279±1 204） and （5 357±1 291 ） μg · L ^-1· h, respectively. The relative bioavailability of test preparation was （100.3±16.2） %. Conclusion The LC-MS/MS method is proven to he accurate, sensitive and convenient, cefdinir in the test suspension is bioequivalent to the reference capsule.