国产盐酸尼卡地平缓释胶囊人体药代动力学及生物利用度

Pharmacokinetics and bioavailability of sustained release capsules of nicardipine hydrochloride in healthy volunteers

目的 比较国产和进口盐酸尼卡地平 (Nic)缓释胶囊的药代动力学及生物利用度。方法 选择 12名健康志愿者随机交叉单剂量及多剂量口服两种Nic缓释胶囊 ,采用GC ECD检测 ,内标法定量测定其血药浓度。结果 两种缓释胶囊空腹给药 ,其单剂量及多剂量达稳态后经时血药浓度均呈双峰曲线 ,国产胶囊单剂量给药的主要参数 :Cmax1( 14 2± 8 2 ) μg·L-1,Cmax2 ( 16 9± 5 8) μg·L-1,Tmax1( 0 79±0 45 )h ,Tmax2 ( 5 0 8± 0 79)h ,T1/2Ke( 5 49± 2 5 3)h ,AUC0～ 2 4 ( 97 9± 2 4 8) μg·h·L-1。多剂量给药的主要参数 :Cmax( 36 7± 6 1) μg·L-1,Cmin( 7 3± 1 6 ) μg·L-1,Cav( 18 9± 3 2 ) μg·L-1,FI( 1 5 6± 0 2 6 ) ,AUC0～ 36( 341 4±48 5 ) μg·h·L-1。国产Nic缓释胶囊单剂量及多剂量给药与进口制剂比较的相对生物利用度各为 97 5 %± 19 3 %和98 2 %± 16 5 %。结论 方差分析及双单侧t检验表明 。

AIM To compared the pharmacokinetics and relative bioavailability between sustained release capsules of domestic and imported nicardipine hydrochloride METHODS Plasma levels of nicardipine was measured by GCECD following a single and multiple oral doses of two capsules(domestic and imported preparations) given to 12 healthy volunteers in a randomized 2way crossover studyRESULTS The concentration versus time curves became bimodal when two sustained release capsules of nicardipine hydrochloride were given before mealsAfter a single oral dose the main pharmacokinetic parameters were C max1 (142±82) and C max2 (169±58) μg·L -1 at (079±045) and (508±079) h, T 1/2Ke (549±253) h,AUC 0～24 (979±248) μg·h·L -1 for domestic capsules Following multiple dosing mean steady state parameter values were C max (367±61) μg·L -1 , C min (73±16) μg·L -1 ,C av (189±32)μg·L -1 , FI (156±026), AUC 0～36 (3414±485) μg·h·L -1 for domestic capsules Relative bioavailabilities of domestic capsules were 975%±193% and 982%±165% compared with imported capsules after a single and multiple oral administration of the two preparations, respectively CONCLUSION The statistic test showed that the pharmacokinetic parameters were no significantly different between the two kind of preparations and bioequivalence of both domestic and imported nicardipine capsules were proved