单剂量头孢克洛缓释片与常释胶囊在健康人体药动学和生物等效性研究

Pharmacokinetics and bioequivalence study of sustained-release tablets and conventional capsules of cefaclor in healthy volunteers

目的了解单剂量头孢克洛缓释片和常释胶囊的药动学特点,评价其生物等效性.方法22名健康男性受试者随机口服头孢克洛缓释片或常释胶囊750mg,定时采集血标本,HPLC法测定血药浓度,按照最佳拟合的方法求算两种药物的药动学参数,评价生物等效性.结果头孢克洛缓释片和常释胶囊的Cmax分别为(7.44±2.77)和(10.11±3.887)mg/L;tmax分别为(3.80±0.87)和(1.42±0.53)h;t1/2β分别为(0.74±0.46)和(0.74±0.19)h;AUC0～n分别为(22.94±5.19)和(23.14±5.41)mg·h/L;AUC0～∞分别为(23.11±5.17)和(23.33±5.497)mg·h/L;CL/F分别为(4.4±1.98)和(6.05±7.49)L/h.F为(101±17.5)%.AUC的双向单侧t检验结果显示两药为生物等效制剂,Cmax和tmax的结果显示头孢克洛缓释片的达峰时间明显滞后于常释胶囊(P＜0.05),血药浓度也明显低于常释胶囊(P＜0.05).结论头孢克洛缓释片和常释胶囊为生物等效制剂,且头孢克洛缓释片在体内确有缓慢释放的特点.

Objective To assess the bioequivalence of sustained-release tablets and conventional capsules of cefaclor in male healthy volunteers. Method An open, randomized, two-way, crossover trial with a one-week washout period was Carried out in 22 volunteers. 750mg dose of sustained-release tablets or conventional capsules of cefaclor was administered. Serum samples were collected at different time intervals and assayed by HPLC method, Bioequivalence was determined by two one-sided t test. Results The Cmax values were （7. 44±2.77） and （10.11±3. 887） mg/L for sustained-release tablets and conventional capsules of cefaclor respectively; tmax were （3.80±0. 87） and （1.42±0.53）h, t1/2β were （0.74±0.46） and （0. 74±0. 19）h, AUC0-n were （22.94±5.19） and （23.14±5.41） mg · h/L; AUC0-∞ were （23. 11±5.17） and （23.33±5. 497） mg/L, respectively; CL/F were （4.4 ± 1.98） and （6.05±7.49） L/h. Relative bioavailability was （101 ± 17.5）%. Two one-sided t test result of AUC showed that two preparations were bioequivalent. But Cmax and tmax, of two preparations were different significantly （P〈0.05）. Conclusion The two preparations were proved to be bioequivalent, and the sustained-release tablets clearly have the characteristic of slow releasing properties.