硫酸沙丁胺醇控释小丸胶囊的人体相对生物利用度研究  

Studies on the relative bioavailability of a novel controlled-release salbutamol capsule in healthy volunteers

作　　者：陈孝[1] 伍杰雄[1] 张霖泽[2] 赵香兰[3] 

机构地区：[1]中山医科大学附属第一医院药学部,广州510080 [2]广州市医药工业研究所,广州510240 [3]中山医科大学临床药理研究所,广州510089

出　　处：《中国现代应用药学》1999年第3期22-25,共4页Chinese Journal of Modern Applied Pharmacy

基　　金：九五国家重点科技项目 (攻关 )计划"缓 (控 )释小丸工业化生产试验研究"专题项目!专题合同编号96-90 2-02-11

摘　　要：目的 :研究硫酸沙丁胺醇控释小丸胶囊和进口控释片及普通片在健康志愿者体内单剂量和多剂量给药后的药代动力学和生物利用度。方法 :8名健康男性志愿者自身随机交叉先后po 8mg受试硫酸沙丁胺醇控释小丸胶囊、沙丁胺醇控释片 (Volmax)或沙丁胺醇普通片 (Ventolin) ,观察其药代动力学和相对生物利用度。另 2 0名受试者自身随机交叉po受试胶囊 ( 8mg ,bid)和Volmax( 8mg ,bid) ,连服 5d ,观察峰谷波动率。用高效液相色谱法测定血药浓度。结果 :单剂量给药后Tmax分别为 ( 4.5± 0 .8)、( 5.0± 1 .5)、( 1 .8± 0 .7)h ;Cmax分别为 ( 1 4 .6± 5.5)、( 1 5.0±3 .8)、( 3 1 .0± 7.5)ng/ml;AUC0～∞ 分别为 ( 1 3 7.4± 3 1 .8)、( 1 3 9.3± 3 1 .4 )、( 1 89.2± 3 1 .3 )ng/ml·h ;MRT分别为( 1 0 .5± 0 .8)、( 1 0 .8± 1 .0 )、( 7.4± 0 .8)h。多剂量给药后第 5天的Tmax分别为 ( 5.5± 0 .8)、( 5.8± 1 .3 )h ;Cmax分别为 ( 1 4 .2± 2 .1 7)、( 1 5.2± 2 .81 )ng/ml;Cmin分别为 ( 7.7± 0 .9)、( 7.8± 1 .1 )ng/ml;AUC0～Tn分别为 ( 1 2 6.5± 1 9.9)、( 1 3 2 .3± 2 2 .1 )ng/ml·h ;峰谷波动率分别为 ( 0 .61± 0 .2 )、( 0 .66± 0 .2 )。结论 :受试胶囊相对于Ventolin和Volmax的生物利用度?OBJECTIVE:To study the pharmacokinetics and relative bioavailability of a novel controlled-release salbutamol capsule.METHOD:The tested controlled-release salbutamol capsule was compared to the inport salbutamol controlled-release formulation-Volmax and the immediate-release formulation of salbutamol-Ventolin to 8 male healthy subjects in a single dose in a randomized three-way crossover design.Another 20 male healthy subjects were enrolled in the multiple oral doses study.Each subject received one 8 mg tested novel controlled-release salbutamol capsule or Volmax every 12 h for 5 consecutive days with 7 days separating each phase.Serum concentrations of salbutamol were determined by HPLC.RESULTS:The pharmacokinetic parameters of the single dose test were listed as follows:T max (4.5±0.8)、(5.0±1.5)、(1.8±0.7)h,C max (14.6±5.5)、(15±3.8)、(31.0±7.5)ng/ml, AUC 0～∞ (137.4±31.8)、(139.3±31.4)、(189.2±31.3)ng/ml·h,MRT(10.5±0.8)、(10.8±1.0)、(7.4±0.8)h,respectively.In the multiple oral doses study,T max was (5.5±0.8)、(5.8±1.3)h respectively,C max was (14.2±2.17)、(15.2±2.81)ng/ml respectively,C min was (7.7 ±0.9)、(7.8±1.1)ng/ml respectively,AUC 0～Tn was (126.5±19.9)、(132.3±22.1)ng/ml·h respectively,and peak-trough fluctuation(PTF) was (0.61±0.2)、(0.66±0.2) respectively.CONCLUSION:The relative bioavailability of the novel controlled-release salbutamol capsule was founded to be 72.4%±10.4% and 99.8%±18.5% compared with Ventolin and Volmax respectively,and it has the distinct characteristics of an effective controlled-release formulation that will offer clinical advantages of better compliance and tolerability over long term usage.

关 键 词：沙丁胺醇 控释胶囊 药代动力学 人体生物利用度 

分 类 号：R974.3[医药卫生—药品] R969.1[医药卫生—药学]