罗红霉素分散片人体相对生物利用度及其药代动力学研究

Relative Bioavailability and Pharmacokinetics of Roxithromycin Dispersive Tablets in Healthy Volunteers

目的 :通过人血清中罗红霉素的微生物测定法 ,考察丽珠集团丽珠制药厂研制的罗红霉素分散片丽珠星相对于法国罗素 优克福公司的罗红霉素普通片罗力得的生物等效性 ,并估算其药代动力学参数。方法 :以藤黄八叠球菌为检定菌 ,通过抑菌圈直径测定血药浓度。临床实验方案采用交叉实验设计 ,10名受试者随机分两组服用罗红霉素分散片和普通片。结果 :本方法日内、日间变异系数均小于 15 % ,线性范围为 0 2 5～ 10 0μg/ml(r =0 9992 ) ,最低检测浓度为 0 2 5 μg/ml。罗红霉素分散片和普通片的主要药动学参数为 :AUC0→ 3 6分别为6 1 4 1± 13 5 3μg·h/ml和 5 7 6 3± 11 2 9μg·h/ml;AUC0→∞ 分别为 6 6 6 2± 17 89μg·h/ml和 6 2 93± 14 6 2 μg·h/ml;cmax分别为 7 15± 0 18μg/ml和 7 37± 0 4 2 μg/ml;tmax分别为 1 10± 0 4 4h和 1 2 0± 0 2 6h ;T1/2 分别为 8 2 1±2 92h和 8 2 8± 2 4 6h。方差分析表明两种制剂的药代动力学参数间均无显著性差异。双单侧t检验表明两制剂吸收程度相同。结论 :本方法简便准确。分散片的相对生物利用度为 (10 5 9± 13 8) % ,表明分散片与普通片吸收程度生物等效。

AIM:To study the pharmacokinetics and relative bioavailability of roxithromycin dispersive tablets in healthy volunteers.METHOD:Following oral administrations of a single dose of 250 mg roxithromycin dispersible tablets(formulation A )and conventional tablets (formulation B)to each of 10 healthy male volunteers in a randomized crossover design.The plasma levels of active drug at different times were determined by a microbial assay with Micrococcus luteus CMCC (B) 28001.RESULT:The AUC 0→36 values of formulation A and B obtained were 61.41±13.53 and 57.63±11.29 μg·h/ml,The AUC 0→∞ values were 66.62±17.89 and 62.93±14.62 μg·h/ml;the t max values were 1.10±0.44 and 1.20±0.26 h;the c max values were 7.15±0.18 and 7.37±0.42 μg/ml,and the t 1/2 values were 8.21±2.92 and 8.28±2.46 h respectively.CONCLUSION:The relative bioavailability of roxithromycin dispersive tablets to conventional tablets was (105.9±13.8)%.The two formulations were bioequivalent.