异丙肌苷片在健康人体内的药动学  

Pharmacokinetic study of inosiplex tablet in healthy volunteers

作　　者：宋薇[1] 杨静[1] 李雪晴[1] 贾艳艳[1] 杨林[1] 周伦[1] 鹿成韬[1] 文爱东[1] 

机构地区：[1]第四军医大学西京医院药剂科,陕西西安710032

出　　处：《中国医院药学杂志》2012年第22期1808-1813,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:探讨健康受试者多次口服异丙肌苷片1 000 mg后体内药动学特点。方法:10例健康受试者,男女各半,每次口服1 000 mg异丙肌苷片,tid,连续7 d,采用液相色谱-串联质谱法(LC-MS/MS)和高效液相色谱法(HPLC)分别测定血浆中N,N-二甲氨基-2-丙醇(Dip)和4-乙酰氨基甲酸(PACBA)的浓度,采用DAS软件计算给药后的药动学参数。结果:单次给药后的主要药动学参如下:Dip的tmax和Cmax分别为(1.55±0.16)h和(2.24±0.18)μg.mL-1;t1/2为(4.42±0.81)h;AUC0-24为(12.93±2.11)μg.h.mL-1;PACBA的tmax和Cmax分别为(1.03±0.51)h和(5.18±1.80)μg.mL-1;t1/2为(0.95±0.13)h;AUC0-24为(7.69±1.13)μg.h.mL-1;多次给药后的主要药动学参如下:Dip的tmax和Cssmax分别为(1.00±0.46)h和(2.49±0.11)μg.mL-1;t1/2为(5.74±1.24)h;AUC0-24为(16.06±2.80)μg.h.mL-1;Cssav为(1.36±0.19)μg.mL-1;DF为1.29±0.31。PACBA的tmax和Cssmax分别为(0.50±0.00)h和(7.37±0.94)μg.mL-1;t1/2为(1.04±0.17)h;AUC0-24为(7.90±1.16)μg.h.mL-1;Cssav为(0.99±0.14)μg.mL-1;DF为7.44±0.90。结论:本测定方法灵敏、准确、简便,多剂量口服异丙肌苷片后Dip及PACBA均有蓄积作用。OBJECTIVE To study the pharmaeokinetics of inosiplex in healthy subjects following multiple dosing of inosiplex tablet. METHODS 10 healthy volunteers （5 females and 5 males） were assigned to receive 1000 mg inosiplex tablet at morning, noon, and evening for consecutive 7 days. The plasma concentrations of N,N-dimethylamino-2 propanol（Dip） and p-acet- aminobenzoie acid （PACBA） were measured by fully validated LC-MS/MS and HPLC method, respectively The pharmacoki- netic parameters were calculated by DAS software. RESULTS The main pharmacokinetic parameters of single dosing of inosi- plex tablet were as follows： for Dip, tmax and Cmax were （ 1.55 ± 0. 16） h and （2. 24±0. 18）μg·mL^-1, respectively; t1/2 was （4. 42 ± 0. 81）h;AUC0-24 was（12. 93±2. 11）μg·h·mL^-1 ;respectively. In the case of PACBA, tmax and Cmax^ss were（1.03 ± 0. 51） h and （5.18±1.80 ）μg·mL^-1, respectively;t1/2 was（0. 95±0. 13）h;AUC0 24 was （7. 69± 1.13）μg·h·mL^-1;The main phar- macokinetic parameters of multiple dosing of inosiplex tablet were as follows： for Dip, tmax and Cmax^ss were （1.00 ± 0. 46）h and （2.49±0. 11）μg·mL^-1, respectively; t1/2 was （5.74 ±1.24）h;AUC0-24 was （16. 06 ± 2. 80）μg·mL^-1 ;Cmax^ss was （1.36 ± 0. 19）μg·mL^-1 ;DF was 1.29 ± 0. 31, respectively. In the case of PACBA, tmax and Cmax^ss were （0. 50 ± 0. 00） h and （7. 37 ± 0. 94） μg·mL^-1, respectively;t1/2 was （1.04± 0. 17） h; AUC0-24 was （7. 90 ±1. 16）μg·h·mL^-1 ;Cmax^ss was （0. 99 ±0. 14）μg·mL^-1 ;DF was 7. 44 ±0. 90. CONCLUSION The method which we developed is sensitive, accurate and simple. And the Dip and PACBA have been accumulated after multi-dosing of inosiplex administration.

关 键 词：异丙肌苷 单次给药 多次给药 药动学 液质联用法 

分 类 号：R969.1[医药卫生—药理学]