氨茶碱贴片的制备及家兔脐部给药的药动学研究  

Preparation of Aminophylline Patches and Their Pharmacokinetics in Rabbits After Navel Adminstration

作　　者：高晓宇[1] 王丛瑶[1] 魏颖慧[1] 徐秀玲[1] 郑杭生[1] 叶姣云[1] 李范珠[1] 

机构地区：[1]浙江中医药大学药学院,杭州310053

出　　处：《中国药学杂志》2012年第23期1925-1930,共6页Chinese Pharmaceutical Journal

基　　金：浙江省卫生高层次创新人才培养对象;浙江省自然科学基金资助(R207722);浙江省中医药管理局项目(2007YA003)

摘　　要：目的制备氨茶碱贴片,并研究其经脐部给药后家兔体内的药动学特征。方法采用流涎工艺制备氨茶碱贴片,以离体大鼠腹部皮肤为透皮屏障,采用改良Franz法优选渗透促进剂。健康家兔分别经灌胃氨茶碱溶液、背部与脐部敷贴氨茶碱贴片后,HPLC测定体内血药浓度,计算药动学参数,评价药动学特征。结果质量分数3%的薄荷脑-丙二醇(1∶1)混合渗透促进剂为药物的最佳渗透促进剂,稳态透皮速率为(9.08±0.21)μg.cm-2.h-1。氨茶碱溶液灌胃、贴剂背部与脐部敷贴后家兔体内的主要药动学参数:ρmax分别为(13.42±1.10)、(4.53±0.39)和(5.77±0.44)μg.mL-1;tmax分别为(1.83±0.29)、(5.67±0.58)和(4.33±0.58)h;AUC0→t分别为(47.65±3.46)、(31.65±4.11)和(39.97±3.14)μg.h.mL-1;t1/2分别为(1.90±0.30)、(2.45±0.07)和(1.90±0.06)h;Ka分别为(2.01±0.55)、(0.33±0.02)和(0.55±0.04)h-1和tlag分别为(0.19±0.04)、(0.59±0.03)和(0.32±0.19)h;以灌胃给药组为对照,背部给药与脐部给药相对生物利用度分别为(67.41±19.11)%、(84.81±18.03)%。结论成功制备了经皮渗透性能良好的氨茶碱贴片。与灌胃给药相比,该贴片经背部、脐部敷贴给药后家兔体内血药峰浓度明显降低,达峰时间延迟;且脐部给药较背部给药生物利用度显著增高,脐部给药有利于氨茶碱经皮吸收。OBJECTIVE To prepare aminophylline patches and study the pharmacokinetic characteristics in rabbits after applica- tion on navel. METHODS Aminophylline patches were prepared by hot-envelop method. Modified Franz diffusion cells were em- ployed to screen permeation enhancers with excised rat abdomen skins as diffusion barrier. The concentration of aminophyHine in rabbit plasma was determined by HPLC after aminophylline solution was irrigated intragastrically and the aminophylline patches were applied on notum and navel, respectively. Pharmacokinetic parameters were calculated and the pharmacokinetic profiles were characterized by comparing the above three groups with statistical analysis. RESULTS Based on the excised rat skin permeation test, 3% menthol- -2 propanediol （1：1 ） mixture was the optimal permeation enhancer with a steady state permeation rate of （9. 08 ± 0. 21 ） μg· cm h^-1. The main pharmacokinetic parameters of, notum application group and navel application group were as follows： Pmax were （13.42±1.10）, （4.53 ±0.39） and （5.77±0.44）μg·mL^-1 andtmax（1.83 ±0.29） , （5.67 ±0.58） and （4.33 ±0.58） h, AUC0-t,（47.65±3.46）, （31.65s4.11） and （39.97 ±3. 14）μg· h · mL^-1,t1/2（1.90±0.30）,（2.45 ±0.07） and （1.90± 0. 06） h, Ka（2. 01 ±0. 55）, （0. 33 ±0. 02） and （0. 55 ±0. 04） h-1, hag were （0. 19 ±0. 04） ,（0. 59 ±0. 03） and （0. 32 ±0. 19） h, respectively. The relative bioavailabilities of aminophylline after notum and navel application were （67.41± 19. 11 ）% and （84. 81± 18.03）% respectively compared with intragastrical irrigation group. CONCLUSION The preparation process of aminophylline patches with desirable skin permeation property is practicable. Aminophylline patches are able to realize sustained-drug release and have higher bioavailability after navel application compared with notum application.

关 键 词：氨茶碱 贴片 渗透促进剂 脐部 药动学 

分 类 号：R969.1[医药卫生—药理学]