药学学报, 2019, 54(6): 1088-1091
引用本文:
郭树攀, 王汝涛, 赵熠, 安龙, 肖飒, 秦燕. 两种晶型异丙双酚片剂的比格犬药代动力学研究[J]. 药学学报, 2019, 54(6): 1088-1091.
GUO Shu-pan, WANG Ru-tao, ZHAO Yi, AN Long, XIAO Sa, QIN Yan. Pharmacokinetics of two types of dipropofol crystal tablets in Beagle dogs[J]. Acta Pharmaceutica Sinica, 2019, 54(6): 1088-1091.

两种晶型异丙双酚片剂的比格犬药代动力学研究
郭树攀1, 王汝涛1, 赵熠1, 安龙1, 肖飒1, 秦燕2
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
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 ±60.26 μg·L-1。药时曲线下面积(AUC0-t)分别为160.49 ±55.26和243.59 ±148.36 μg·L-1·h。晶型Ⅱ的AUC0-tCmax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。
关键词:    异丙双酚      晶型      药代动力学      HPLC-MS/MS     
Pharmacokinetics of two types of dipropofol crystal tablets in Beagle dogs
GUO Shu-pan1, WANG Ru-tao1, ZHAO Yi1, AN Long1, XIAO Sa1, QIN Yan2
1. Xi'an Libang Zhaoxin Biological Technology Co., Ltd, Xi'an 710077, China;
2. Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China
Abstract:
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 ±20.16 μg·L-1 after 20 mg·kg-1 crystal form Ⅰ tablet taken orally, and the AUC0-t was 160.49 ±55.26 μg·L-1·h. After 20 mg·kg-1 crystal form Ⅱ tablet taken, the Cmax of dipropofol was 92.58 ±60.26 μg·L-1, and the AUC0-t was 243.59 ±148.36 μg·L-1·h. The AUC0-t and Cmax of crystal form Ⅱ were significantly different from that of crystal form Ⅰ (P<0.05). Crystal form Ⅱ was the dominant crystal form. The results suggest that we should control crystal form during the development of dipropofol oral tablets.
Key words:    dipropofol    crystal tablets    pharmacokinetics    HPLC-MS/MS   
收稿日期: 2019-01-17
DOI: 10.16438/j.0513-4870.2019-0061
基金项目: 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).
通讯作者: 郭树攀
Email: guoshupang2589@163.com
相关功能
PDF(930KB) Free
打印本文
0
作者相关文章
郭树攀  在本刊中的所有文章
王汝涛  在本刊中的所有文章
赵熠  在本刊中的所有文章
安龙  在本刊中的所有文章
肖飒  在本刊中的所有文章
秦燕  在本刊中的所有文章

参考文献:
[1] Threlfall TL. Analysis of organic polymorphs[J]. Analyst, 1995, 120:2435-2460.
[2] Clas SD. The importance of characterizing the crystal form of the drug substance during drug development[J]. Curr Opin Drug Discov Devel, 2003, 6:550-560.
[3] Yu LX, Furness MS, Raw A, et al. Scientific considerations of pharmaceutical solid polymorphism in abbreviated new drug applications[J]. Pharm Res, 2003, 20:531-536.
[4] Byrn S, Pfeiffer R, Ganey M, et al. Pharmaceutical solids:a strategic approach to regulatory considerations[J]. Pharm Res, 1995, 12:945-954.
[5] Ma LW, Du W, Zhao CS. Advances in the quantitative analytical methods of drug polymorphism[J]. Acta Pharm Sin (药学学报), 2011, 46:896-903.
[6] Du GH, Lv Y. Optimal drug polymorphism of solid compound[J]. Chin Pharm J (中国药学杂志), 2010, 45:5-11.
[7] Fang LH, He GR, Wang HY. Strategy of compound polymorph bioactivity study in early druggability evaluation[J]. Chin Pharm J (中国药学杂志), 2013, 48:497-500.
[8] Wang RT, Chen T, Hu HJ, et al. Application of dipropofol and its derivatives in the treat of epilepsy:CN, ZL201010160034.9[P]. 2010-08-08[2018-10-10].
[9] Zhang JL, Chen XL, K M, et al. Anticonvulsant effect of dipropofol by enhancing native GABA currents in cortical neurons in mice[J] Nervous System Pathophysiol, 2018, 120:1404-1414.
[10] Wang RT, Chen T, Wang WJ. The crystal forms and preparation methods of 3,3',5,5'-tetraisopropyl-4,4'-diphenyl:CN, ZL201310055828.2[P]. 2013-07-03[2018-10-10].
[11] Shi JM, Han WL, Chen LY, et al. HPLC-MS/MS determination and pharmacokinetic study of propofol in human plasma[J]. Pharm Anal, 2012, 32:1136-1142.
[12] Sun XQ, Ma JS. Simultaneous determination of carbamazepine and phenobarbital in human plasma by UPLC-MS/MS[J]. China Pharm (中国药师), 2016, 19:1826-1830.
[13] Lee SH, Park HW, Kim MJ. External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long-chain triglyceride emulsion propofol in Beagle dogs[J]. Vet Pharmacol Ther, 2012, 35:329-341.
相关文献:
1.王蕊, 王宝莲, 李燕.HPLC-MS/MS法研究恒河猴口服新型调血脂化合物IMM-H007后的全血药代动力学特征[J]. 药学学报, 2018,53(7): 1156-1161
2.陈帅, 夏媛媛, 魏广力, 李全胜, 刘梦杰, 陈勇, 司端运.柱前衍生化结合UHPLC-MS/MS法同时测定Beagle犬血浆中的红景天苷和酪醇[J]. 药学学报, 2017,52(2): 296-301
3.秦至臻, 陈芊茜, 宋俊科, 吕扬, 杜冠华.奥扎格雷两种晶型在大鼠体内的药代动力学研究[J]. 药学学报, 2015,50(2): 218-221
4.王宝莲, 扈金萍, 盛 莉, 陈 晖, 李 燕.HPLC-MS/MS法定量研究比格犬灌胃替诺福韦酯后替诺福韦血浆药代动力学[J]. 药学学报, 2013,48(3): 390-394
5.于晓彦 陈芊茜 白晓宇 田硕 孙加琳 吕扬 杜冠华.大鼠口服硫酸氢氯吡格雷的多晶型吸收特点研究[J]. 药学学报, 2011,46(10): 1268-1272
6.徐晓燕;张蕊;袁桂艳;王本杰;刘晓燕;郭瑞臣.HPLC-MS/MS法测定人体色甘酸钠血浆浓度及其药代动力学研究[J]. 药学学报, 2008,43(9): 942-945
7.孔爱英;张振清;乔建忠;张帆;周文霞;刘克良;阮金秀.HPLC-MS/MS法测定血浆中十肽化合物LXT-101及Beagle犬药代动力学研究[J]. 药学学报, 2008,43(9): 946-950
8.张蕊;王本杰;赵恒利;李小利;魏春敏;郭瑞臣.HPLC-MS/MS法测定血浆中莪术醇浓度及Beagle犬体内的药代动力学研究[J]. 药学学报, 2007,42(9): 973-977