丙戊酸钠缓释片及其人体生物利用度的研究  

Preparation of Sodium Valproate Sustained-Release Tablets and Evaluation on its Bioavailability in Healthy Volunteers

作　　者：戈文兰[1] 王广基[2] 孙建国[2] 郁健[3] 何海燕[4] 郭建兰[1] 

机构地区：[1]江苏省药物研究所 [2]中国药科大学药代研究中心 [3]中国药科大学药物分析教研室,南京210009 [4]江苏省药物研究所药物分析教研室,南京210009

出　　处：《中国药科大学学报》2000年第6期422-425,共4页Journal of China Pharmaceutical University

摘　　要：制备了丙戊酸钠缓释片（SRT），其释放曲线与国外缓释片（ Depakine Chrono.简称DC）基本一致。对SRT和普通片（CT）进行人体生物利用度比 较，10名健康男性志愿者随机交叉口服单剂量两种剂型后，利用HPLC测得血药浓度。SRT和C T的AUC分别为1143.6±139.6 μg·h/ml和1082.7±205.5 μg·h/ml，MRT分别为22.6 ±3.8 h和18.8±3.6 h，Cmax分别为47.7±7.5 μg/ml和67.0±8.6 μg/ml，T max分别为6.2±1.4 h和1.6±0.9 h。SRT的相对生物利用度为107.0%±10.7%。与CT相 比，SRT能明显推迟达峰时间并降低峰浓度（P<0.01），AUC无显著性差异（Ｐ>0.0 5）。10名受试者多剂量服用SRT和CT后，稳态时Cmin分别为91.8±14.7 μg/ml 和83.2±24.4 μg/ml，Cmax分别为134.4±23.2 μg/ml和134.4±38.3 μg/ml ，波动系数FI分别为0.374±0.092和0.483±0.162。Sodium Valproate Sustained-release tablets (SRT) were prepared. T he release curves of SRT were consistent with Depakine Chrono (DC). The pharmaco kin etics and bioavailability of SRT was evaluated using the conventional tablets ( CT). The plasma concentrations were determined by HPLC after a randomized crosso ver oral administration of single dose of SRT and CT in 10 healthy volunteers. The pharmacokinetic parameters of AUC0→∞、MRT、Cmax and Tmax were:SRT:1143.6±139.6 μg/ml·h、22.6±3.8 h、47.7±7.5 μg/ml、6.2 ±1.4 h; CT:1082.7±205.5 μg/ml·h、18.8±3.6 h、67.0±8.6 μg/ml、1.6±0.9h. It was found that the mean Cmax for SRT was significantly lower than that for CT (Ｐ<0.01) and the mean Tmax was significantly later for SRT than that for CT. The total area under the plasma concentration-time curve was not significantly different between these two preparations (Ｐ>0.05).The relative bioavailability of SRT was 107.0%±10.7%. After multiple dosing in 10 healthy volun t eers, the mean steady state Cmin values were 91.8±14.7 μg/ml and 83. 2±24.4 μg/ml, the mean Cmax values were 134.4±23.2 μg/ml and 134.4 ±38.3 μg/ml respectively. The fluctuation indexes (FI) for the two preparations were 0.374 ±0.092 and 0.483±0.162. The results showed that the two preparations were bioequivalent.

关 键 词：丙戊酸钠 缓释片 药代动力学 相对生物利用度 

分 类 号：R944[医药卫生—药剂学]