匹多莫德口服液及其不同剂型的固体制剂在Beagle犬体内药代动力学比较研究  

Pharmacokinetics and bioavailability of pidotimod in Beagle dog after oral solution and different solid preparations

作　　者：沈博宇 李昊丰 殷小茜 朱璋佩 李昔诺 王广基[1] 梁艳[1] SHEN Boyu;LI Haofeng;YIN Xiaoxi;ZHU Zhangpei;LI Xinuo;WANG Guangji;LIANG Yan(Key laboratory of Drug Metabolism ＆ Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu, China)

机构地区：[1]中国药科大学药物代谢动力学重点实验室

出　　处：《中国临床药理学与治疗学》2017年第9期1012-1016,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(81573559;81273589)

摘　　要：目的:通过研究江苏吴中医药集团有限公司生产的匹多莫德口服液(芙露饮)和意大利多帕药业原研的匹多莫德口服液(普利莫)在Beagle犬体内的药代动力学特征,计算芙露饮的相对生物利用度,考察其与普利莫在Beagle犬体内的生物等效性。然后通过研究匹多莫德片剂、颗粒剂、胶囊和分散片在Beagle犬体内的药代动力学,考察剂型对匹多莫德在Beagle体内生物利用度的影响。方法:14只Beagle犬进行随机双交叉试验,清洗期为一周,分别给予400 mg匹多莫德芙露饮口服液、普利莫口服液匹多莫德片剂、颗粒剂、胶囊和分散片,采用LC-MS/MS测定Beagle犬血浆中匹多莫德浓度,并以DAS 2.0软件计算药代动力学参数,考察不同剂型的匹多莫德在Beagle犬体内的药代动力学特征。结果:Beagle犬灌胃给予400 mg江苏吴中医药集团有限公司生产的匹多莫德口服液"芙露饮"后的药代动力学参数为:t1/2:(3.88±0.77)h,Cmax:(23 367±5 298)ng/m L,Tmax:(1.1±0.5)h,AUC0-τ:(93 948±28 016)ng·h·m L^(-1);Beagle犬灌胃给予400 mg意大利多帕药业生产的匹多莫德口服液"普利莫"后的药代动力学参数为:t1/2:(3.50±0.36)h,Cmax:(21 233±5 542)ng/m L,AUC0-τ:(83 032±20 539)ng·h·m L^(-1);匹多莫德片在Beagle犬体内的药代动力学参数为:t1/2:(4.04±1.16)h,Cmax:(18 150±4 510)ng/m L,AUC0-τ:(71 966±20 652)ng·h·m L^(-1);匹多莫德颗粒剂在Beagle犬体内的药代动力学参数为:t1/2:(3.52±0.49)h,Cmax:(17 750±3 558)ng/m L,AUC0-τ:(70 203±18 330)ng·h·m L^(-1);匹多莫德胶囊的药代动力学参数为:t1/2:(4.38±2.24)h,Cmax:(19 225±3 205)ng/m L,AUC0-τ:(70 199±11 618)ng·h·m L^(-1);匹多莫德分散片的药代动力学参数为:(3.88±0.53)h,Cmax:(18 400±2 439)ng/m L,AUC0-τ:(71 088±11 224)ng·h·m L^(-1)。结论:江苏吴中医药集团有限公司生产的匹多莫德口服液"芙露饮"和意大利多帕药业生产的"普利莫"在Beagle犬体内生物等效,各固体制剂在BeagleAIM ： To vailability of the two kinds （Fulu-Yin and Polimod） investigate the bioequia- of pidotimod oral solution which produced by Jiang- su Wuzhong Pharmaceutical Group Co. , Ltd and Italy Duopa pharmaceutical company, respectively, and to explore the influence of dosage forms on bioavailability of pidotimod via comparing the pharma- cokinetics and relative bioavailability of pidotimod tablet, granules, capsules and dispersible tablets in beagle dogs. METHODS： Beagle dogs were orally administrated 400 mg of pidotimod oral solution Fu- lu-Yin and Polimod and the four kinds pidotimod solid preparations, respectively. After quantitatively measuring the concentrations of pidotimod in plasma, the pharmacokinetic parameters and relative bioavailability of Polimod, pidotimod tablet, gran- ules, capsules and dispersible tablets were calculated and compared with those of Fulu-Yin to investi-gate the bioequiavailability of different dosage forms of pidotimod. RESULTS ： The pharmacokinetic parameters of the pidotimod after ig administration of 400 mg of Fulu-Yin were as follows ： t1/2 was （3.88 ±0.77） h, Cm,x was （23367 ±5298） ng/mL, Tmaxwas （1.1 ±0.5） h, AUC0-T was （93948 ± 28 016） ng·h·m L^-1. The pharmaeokinetie param- eters of the pidotimod after ig administration of 400 mg of Polimod were as follows： t1/2 was （3.50 ± 0.36） h, Cmax was （21233 ± 5542） ng/mL, AUC0-T, was （83 032 ±20 539） ng·h·m L^-1. Besides, the pharmacokinetie parameters the pidotimod have no significant difference after ig administration of 400 mg of pidotimod tablet, granules, eapsules and dispersible tablets. CONCLUSION： The phar- maeeutieal Fulu-Yin and Polimod were bioequivalent in Beagle dogs, and the pidotimod oral liquid had higher bioavailability than pidotimod tablet, granules, capsules and dispersible tablets.

关 键 词：匹多莫德 生物等效性 芙露饮 普利莫 固体制剂 

分 类 号：R969.1[医药卫生—药理学]