两种晶型异丙双酚片剂的比格犬药代动力学研究  

Pharmacokinetics of two types of dipropofol crystal tablets in Beagle dogs

作　　者：郭树攀 王汝涛 赵熠 安龙 肖飒 秦燕[2] GUO Shu-pan;WANG Ru-tao;ZHAO Yi;AN Long;XIAO Sa;QIN Yan(Xi'an Libang Zhaoxin Biological Technology Co.,Ltd,Xi'an 710077,China;Shanghai Institute of Pharmaceutical Industry,Shanghai 200437,China)

机构地区：[1]西安力邦肇新生物科技有限公司,陕西西安710077 [2]上海医药工业研究院,上海200437

出　　处：《药学学报》2019年第6期1088-1091,共4页Acta Pharmaceutica Sinica

基　　金：国家科技重大专项“重大新药创制”“以离子通道为靶标的重大新药创制”(2014ZX09507003-005)

摘　　要：本研究利用HPLC-MS/MS建立了比格犬血浆中异丙双酚的测定方法,并研究了异丙双酚两种晶型片剂在比格犬体内的药代动力学特性。本研究所涉及的动物实验获得了上海医药工业研究院药理评价研究中心实验动物管理和福利、伦理委员会批准。结果显示比格犬口服异丙双酚晶型Ⅰ和Ⅱ片剂各20 mg·kg^-1后,血浆中异丙双酚最大血药浓度(Cmax)分别为69.02±20.16和92.58±60.26μg·L^-1。药时曲线下面积(AUC0-t)分别为160.49±55.26和243.59±148.36μg·L^-1·h。晶型Ⅱ的AUC0-t和Cmax与晶型Ⅰ相比有显著差异(P<0.05),晶型Ⅱ为优势晶型,提示在异丙双酚口服剂型制备时要注意晶型的控制。A method for determining dipropofol in the plasma of Beagle dogs was established by HPLC-MS/MS.We also studied the pharmacokinetic characteristics of two different forms of crystal tablets of dipropofol in Beagle dogs.All animal experiments were approved by the Animal Experimental Management,Welfare and Ethics Committee of Pharmacology Evaluation Research Center,Shanghai Institute of Pharmaceutical Industry.The results indicate that the maximum plasma concentration(Cmax)of dipropofol was 69.02±20.16μg·L^-1 after20 mg·kg^-1 crystal formⅠtablet taken orally,and the AUC0-twas 160.49±55.26μg·L^-1·h.After 20 mg·kg^-1 crystal formⅡtablet taken,the Cmaxof dipropofol was 92.58±60.26μg·L^-1,and the AUC0-twas 243.59±148.36μg·L^-1·h.The AUC0-tand Cmaxof crystal formⅡwere significantly different from that of crystal formⅠ(P<0.05).Crystal formⅡwas the dominant crystal form.The results suggest that we should control crystal form during the develop‐ment of dipropofol oral tablets.

关 键 词：异丙双酚 晶型 药代动力学 HPLC-MS/MS 

分 类 号：R917[医药卫生—药物分析学]