阿仑膦酸钠肠溶片和普通片的人体尿药排泄动力学比较  

Comparison of alendronate sodium enteric and normal tablets in human urine excretion

作　　者：韩睿[1] 孙德助[1] 苏浩明[1] 邵方娴[1] 金婵[1] 高荧[1] 杭太俊[1] 宋敏[1] 陶蕾 李琳珺 马鹏程 

机构地区：[1]中国药科大学药物分析室,南京210009 [2]中国医学科学院皮肤病医院,南京210042

出　　处：《中国新药杂志》2012年第19期2292-2296,共5页Chinese Journal of New Drugs

摘　　要：目的:建立人尿液中阿仑膦酸钠的芴甲氧羰酰氯(Fmoc-Cl)衍生化HPLC-荧光检测法,用于阿仑膦酸钠肠溶片和普通片的人体药代动力学比较研究。方法:20名男性健康志愿者分别给药70 mg阿仑膦酸钠肠溶片或普通片,采集0～24 h内不同时间段的尿液样本,帕米膦酸钠内标法测定受试者尿液阿仑膦酸钠浓度并计算排泄量,DAS 2.1软件计算尿液排泄动力学参数。结果:阿仑膦酸钠浓度在1～500 ng.mL-1范围响应与浓度呈良好的线性关系(r>0.990 0)。批内及批间精密度和准确度均符合要求。阿仑膦酸钠普通片和肠溶片的尿药累积排泄量分别是(466±261)和(306±234)μg,最大排泄速率分别是(190±118)和(86±57)μg.h-1。结论:建立的测定法专属耐用灵敏度适宜,阿仑膦酸钠肠溶片与普通片剂相比,药代动力学行为发生明显改变。Objective： To establish an HPLC florescence detection method for assay of alendronate in human urine samples after Fmoc derivatization and application, and to compare pharmacokinetics of alendronate sodium enteric and normal tablets in healthy Chinese volunteers. Methods： An open labeled, randomized, and twotreatment study was conducted in 20 healthy male Chinese volunteers. They orally took a single dose of either 70 mg enteric or normal tablets. The urine samples were collected in predetermined time intervals up to 24 h. The alendronate sodium concentrations in urine were determined by the HPLC florescence detection method with pamidronate as the internal reference standard. The cumulative urine excretions were calculated. The urine pharmacokinetic pa- rameters were calculated by DAS 2.1 software. Results： The linear calibration curves were established for the derivative HPLC florescence detection of urine alendronate sodium in the range of 1 to 500 ng· mL^- 1 （r 〉 0. 990 0）. The intra- and inter-batches precision and accuracy, expressed as the relative standard deviation （RSD%） and the relative error （RE%） , were within the criteria limits for bioassay. The cumulative urine excretions of the enteric and normal tablets were （466 ±261 ） and （306 ±234） μg with the peak excretion rate of （190 ± 118） and （86 ± 57 ） μg· h^-1 , respectively. Conclusion： The established HPLC method is selective, rugged and suitable for the bioassay. There are obvious pharmacokinetic differences between the alendronate sodium enteric and normal tablets.

关 键 词：阿仑膦酸钠 尿样 药代动力学 芴甲氧羰酰氯衍生化 HPLC-荧光检测法 

分 类 号：R969.1[医药卫生—药理学]