克拉霉素胶囊的药动学与相对生物利用度

 目的：研究克拉霉素胶囊在正常人体内的药动学与相对生物利用度。方法：以藤黄八叠球菌28001为敏感菌株，采用微生物法测定10名健康志愿受试者 po 单剂量克拉霉素胶囊和进口片剂(500 mg)后血清中克拉霉素的浓度；以PKBP-Nl程序处理测定结果，计算药动学参数；用双单侧t检验法和配对t检验法对主要的药动学参数进行统计分析，评价二者的生物等效性。结果：微生物法的最低检浏浓度为0.05μg·ml^-1，线性范围0.05～4.00μg·ml^-1，回收率为99.04%～101.48%，RSD≤8.20%；克拉霉素在人体内的药动学行为均符合一级吸收的开放一室模型，二者的达峰时间分别为(1.45土0.50)h和(1.55士0.44)h，峰浓度分别为(2.20±0.39)μg·ml^-1和((2.15士0.33)μg·ml^-1，血浓经时曲线下面积分别为(17.60士2.85)μg·ml^-1和(17.74±3.46)μg·ml^-1。结论：以克拉霉素进口片为参比，计算得克拉霉素胶囊的相时生物利用度为101.64%，二者生物等效。

Pharmacokinetics and relative bioavailability of clarithromycin capsule

OBJECTIVE: To study the pharmacokinetics and relative bioavailability of clarithromycin capsule. METHODS: A microbiological agar diffusion assay using Micrococcus luteus(ATCC 28001) was used as a bioassay for clarithromycin in serum following a single oral dose 500 mg of clarithromycin capsule and tablet respectively given to 10 healthy volunteers in an open randomized cross over test.The data obtained were fitted with PKBP-N1 program. RESULTS: A linear relationship was obtained between the peak area ratio and the concentration of clarithromycin from 0.05 to 4.00 μg·ml_-1and the lowest limit of detection of clarithromycin in serum was 0.05 μg·ml_-1Precisions were under 8.20%.The recoveries were 99.04%～101.48%.The one compartment open model with first order absorption was used to described the time course of serum concentrations of clarithromycin in human following administration of a single oral dose 500 mg as capsule and tablet.The results were t_peak=(1.45±0.50) h and (1.55±0.44) h,c_max=(2.20±0.39) μg·ml_-1and (2.15±0.33) μg·ml_-1,AUC=(17.60±2.85) μg·h·ml_-1 and (17.74±3.46) μg·h·ml_-1. CONCLUSION: There were no significant differneces between their pharmacokinetic parameters.The tested capsule and the reference tablet is bioequivalent with F_rel=101.64%.