尼莫地平缓释片在中国健康人体的生物等效性  

Bioequivalence of nimodipine sustain-released tablets in Chinese healthy volunteers

作　　者：郑萍[1] 许重远[2] 罗荣城[2] 张甫婷[2] 马安德 陈凌云[3] 

机构地区：[1]南方医科大学南方医院药学部,广州510515 [2]南方医科大学南方医院I期研究室,广州510515 [3]南方医科大学公共卫生与热带医学学院卫生检测中心,广州510515

出　　处：《中国临床药理学杂志》2010年第12期899-903,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究尼莫地平(抗缺血性脑损伤药)缓释片的相对生物利用度,并评价其生物等效性。方法采用随机交叉试验设计,20名中国健康男性志愿者分别单次和多次口服尼莫地平缓释片受试制剂与参比制剂,用液相色谱-串联质谱法测定血浆中尼莫地平的血药浓度,计算药代动力学参数及相对生物利用度。结果单次口服2种尼莫地平缓释片,受试制剂和参比制剂的主要药代动力学参数:tmax分别为(2.63±0.71),(2.88±0.79)h;Cmax分别为(13.18±5.21),(13.05±5.11)μg.L-1;t1/2分别为(3.15±0.79),(3.34±1.10)h;MRT0-t分别为(5.58±0.93),(5.78±1.06)h;MRT0-∞分别为(5.93±0.89),(6.24±1.14)h;AUC0-t分别为(73.84±28.09),(76.85±30.09)μg.h.L-1;AUC0-∞分别为(75.24±28.18),(78.58±30.08)μg.h.L-1;F为(97.70±12.10)%。连续多次口服2种尼莫地平缓释片,给药第3d血药浓度达稳态后,受试制剂和参比制剂主要药代动力学参数:tmax分别为(2.43±0.37),(2.40±0.38)h;Css-max分别为(17.51±4.22),(16.52±4.16)μg.L-1;Css-min分别为(3.58±1.92),(2.96±1.67)μg.L-1;Cav分别为(7.29±1.97),(7.23±2.15)μg.L-1;t1/2分别为(4.10±1.42),(3.78±1.09)h;MRT0-t分别为(5.63±0.82),(5.71±0.92)h;MRT0-∞分别为(6.65±1.47),(6.37±0.96)h;AUCss分别为(87.44±23.69),(86.74±25.75)μg.h.L-1;DF分别为(1.99±0.72),(1.96±0.68);F为(102.20±10.70)%。结论受试制剂与参比制剂具有生物等效性。Objective To investigate the bioavailability and the bioequivalence of nimodipine sustain-released tablets.Methods Twenty Chinese healthy male volunteers were divided into two groups by an open,randomized two period crossover with fourteen days washout in trials.A single or multiple oral doses were given to the volunteers.Nimodipine sodium concentrations were assayed by the LC-MS/MS method,and calculated pharmacokinetic parameters and bioavailability.Results The main pharmacokinetic parameters of test and reference nimodipine sustain-released tablets obtained from single oral dose were as follows：tmax were（2.63±0.71）,（2.88±0.79）h;Cmax were（13.18±5.21）,（13.05±5.11）μg·L-1;t1/2 were（3.15±0.79）,（3.34±1.10）h;MRT0-t were（5.58±0.93）,（5.78±1.06）h;MRT0-∞ were（5.93±0.89）,（6.24±1.14）h;AUC0-t were（73.84±28.09）,（76.85±30.09）μg·h·L-1;AUC0-∞ were（75.24±28.18）,（78.58±30.08）μg·h·L-1;F of the test and reference was（97.70±12.10）%,respectively.The steady-state pharmacokinetic parameters were as follows：tmax were（2.43±0.37）,（2.40±0.38）h;Css-max were（17.51±4.22）,（16.52±4.16）μg·L-1;Css-min were（3.58±1.92）,（2.96±1.67）μg·L-1;Cav were（7.29±1.97）;（7.23±2.15）μg·L-1;t1/2 were（4.10±1.42）,（3.78±1.09）h;MRT0-t were（5.63±0.82）,（5.71±0.92）h;MRT0-∞ were（6.65±1.47）,（6.37±0.96）h;AUCss were（87.44±23.69）,（86.74±25.75）μg·h·L-1;DF were（1.99±0.72）,（1.96±0.68）;F was（102.20±10.70）%,respectively.Conclusion The result indicated that the two sustain-released tablets were bioequivalent in healthy volunteers.

关 键 词：尼莫地平缓释片 生物等效性 液相色谱-串联质谱 

分 类 号：R969.1[医药卫生—药理学] R972.4[医药卫生—药学]