利鲁唑片在健康男性人体内生物等效性研究

目的: 建立利鲁唑片生物浓度的固相萃取后HPLC-UV 检测方法, 研究其在健康男性人体内药代动力学和相对生物利用度。方法: 20 名健康男性志愿者单剂量随机交叉口服150 mg 利鲁唑片剂和进口参比制剂后于不同时间点静脉取血, 血浆经固相萃取, 甲醇洗脱吹干后用少量甲醇溶解后, 采用高效液相色谱-紫外检测器, 应用内标法计算利鲁唑浓度。结果: 利鲁唑片与参比制剂的主要药动学参数C_max 分别为930 ±321 和798 ±306 μg·L^-1, t_max 分别为0. 8 ±0. 5 和1. 2 ±0. 7 h, AUC_{0 ～ t} 分别为3361 ±890和3301 ±886 μg·h^-1·L^-1,AUC_{0 ～ ∞}分别为3661 ±886和3614 ±885 μg·h^-1·L^-1, t_1/2 分别为8. 2 ±2. 8 和8. 1 ±2. 6 h 。AUC_{0 ～ t} 和C_max 的90 %置信区间为:96. 11 %～ 107. 77 %和101. 6 % ±135. 9 %。AUC_{0～ t} 相对生物利用度为102. 8 %±15. 5 %。结论: 国产利鲁唑片剂和进口片两种制剂生物等效。

Bioequivalence of riluzole in healthy male volunteers

AIM: To develop a HPLC-UV method to determine the concentration of riluzole in human plasma and study its bioequivalence.METHODS: Single oral dose (150 mg)of riluzole (national procted and import) was given to 20 healthy male volunteers in a randomized cross-over study. Riluzole was extracted from plasma by solid-phase extraction and assaved by a validated highperformance liquid chromatography (HPLC)method with UV detection. Plasma samples (1. 0 ml) applied to a 1 ml C18 solid phase columns. The columns were washed sequentially with distilled water (1ml), and 30 %(volume/volume)methanol. The samples were eluted with 1 ml methanol and dried under a stream of nitrogen. The samples were applied to the HPLC in little methanol. Riluzole was isolated then and detected by UV absorption of 265 nm.Variance analysis and two-one sided test statistical analysis were performed for pharmacokinetic parameters.RESULTS: The main pharmacokinetic parameters of riluzole (the national procted and import)were as follows: C_max: 930 ±321 μg·L^-1 and 798 ±306 μg·L^-1; t_max: 0. 8 ±0. 5 and 1. 2 ±0. 7 h; AUC_{0 ～ t} 3361 ±890 μg·h^-1 ·L^-1 and 3301 ±886 μg·h^-1 ·L^-1; AUC_{0 ～ ∞}: 661 ±886 μg·h^-1·L^-1 and 3615 ±885 μg·h^-1·L^-1; t_1/2:8. 2 ±2. 8 and 8. 1 ±2. 6 h. The relative bioavailability of AUC_{0～ 36} was (102. 8 ± 15. 5)%.CONCLESION: The two formulations were bioequivalent.