3种新型盐酸吡格列酮共晶在大鼠体内的药动学  

Pharmacokinetics of three new cocrystals of pioglitazone hydrochloride in rats

作　　者：孔德文 房政钰 龚宁波[2] 王英 杜立达 张森 蒋楠 杨海光 方莲花 吕扬[2] 杜冠华 KONG De-wen;FANG Zheng-yu;GONG Ning-bo;WANG Ying;DU Li-da;ZHANG Sen;JIANG Nan;YANG Hai-guang;FANG Lian-hua;LV Yang;DU Guan-hua(Bejing Key Laboratory of Drug Targets Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Research Centre of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Bejing 100050,China;Shandong Jishi Pharmaceutical Co.,Ltd.,Jinan 250101,China;School of Pharmacy,Henan University,Kaifeng 475004,China)

机构地区：[1]中国医学科学院北京协和医学院药物研究所国家药物筛选中心,药物靶点研究和新药筛选北京市重点实验室,北京100050 [2]中国医学科学院北京协和医学院药物研究所药物晶型中心,晶型药物研究北京市重点实验室,北京100050 [3]山东济世药业有限公司,济南250101 [4]河南大学药学院,开封475004

出　　处：《中国新药杂志》2023年第10期1057-1063,共7页Chinese Journal of New Drugs

基　　金：中国医学科学院医学与健康科技创新工程基金资助项目(2021-I2M-1-005);山东省重点研发计划资助项目(2019JZZY020909)。

摘　　要：目的:评价3种盐酸吡格列酮(pioglitazone hydrochloride,PGH)共晶在SD大鼠体内的生物吸收过程,改善PGH水溶性差、生物利用度低等问题。方法:采用悬浮液法制备得到盐酸吡格列酮-对氨基苯甲酸、盐酸吡格列酮-对氨基水杨酸和盐酸吡格列酮-没食子酸3种新型共晶物质,通过多种分析检测技术进行表征,并采用HPLC-MS法测定大鼠血浆中PGH浓度,分析大鼠口服PGH共晶后的药动学参数。结果:3种共晶均具有良好的稳定性和溶解度,其中盐酸吡格列酮-对氨基苯甲酸和盐酸吡格列酮-没食子酸2个共晶能够改善大鼠口服PGH的生物利用度、达峰浓度(peak concentration,C_(max))和血药物浓度-时间曲线下面积(area under the cure,AUC)。结论:共晶技术是改变药物PGH溶解度和体内吸收特点的一种重要方法。Objective:To evaluate the absorption of pioglitazone hydrochloride(PGH)cocrystals in SD rats and improve the problems of poor solubility and low bioavailability of PGH.Methods:Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid,pioglitazone hydrochloride-para-aminosalicylic acid and pioglitazone hydrochloride-gallic acid were prepared by suspension method.PGH and 3 cocrystals were characterized by a variety of analytical techniques,and the concentration of PGH in rat plasma was determining by high performance liquid chromatography-mass spectrometry(HPLC-MS)to analyze the pharmacokinetic parameters of cocrystals.Results:The 3 cocrystals all showed good stability and solubility.Cocrystals of pioglitazone hydrochloride-para aminobenzoic acid and pioglitazone hydrochloride-gallic acid could significantly improve the bioavailability,peak concentration(C_(max)),and area under the curve(AUC)of oral PGH in rats.Conclusion:Cocrystallization is an important method to change PGH solubility and absorption characteristics in vivo.

关 键 词：盐酸吡格列酮 共晶化合物 高效液相质谱法 药动学 血药浓度 

分 类 号：R944[医药卫生—药剂学]