唑类抗真菌药物手性分离及药代动力学研究进展

郭凯欣; 石宽; 闻俊; 周婷婷; 范国荣

doi:10.3969/j.issn.1006-0111.2012.06.006

唑类抗真菌药物手性分离及药代动力学研究进展

doi: 10.3969/j.issn.1006-0111.2012.06.006

1.
第二军医大学药学院药物分析学教研室, 上海 200433;解放军75215部队卫生队, 广东惠州 516133
2.
第二军医大学药学院药物分析学教研室, 上海 200433;解放军95890部队卫生队, 湖北武汉 434000
3.
第二军医大学药学院药物分析学教研室, 上海 200433;上海市药物(中药)代谢产物研究重点实验室, 上海 200433

基金项目: 国家自然科学基金(81001420),上海市教委重点课程建设项目(药物分析学).

Advance in chiral separation and stereo selectivity pharmacokinetics of azole antifungal drugs

1.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China;Medical Team, 75215 Force, Huizhou 516133, China
2.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China;Medical Team, 95890 Force, Wuhan 434000, China
3.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China;Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Shanghai 200433, China

摘要: 唑类抗真菌药物具有手性特征,给药后体内对映体血药浓度及药动学参数显示出差异,具有立体选择性特点,代谢是导致该类药物呈现立体选择性变化的主要环节。而生物样本中对映体定量分析则依赖于手性拆分技术的不断发展。本文综述了近年来唑类抗真菌药物主要手性分析技术及酮康唑、伊曲康唑手性药代动力学研究进展,以期为唑类抗真菌新药研究提供参考。
- 唑类抗真菌药物 /
- 手性分离 /
- 药代动力学 /
- 立体选择性
Abstract: Generally azole antifungal drugs possessed chiral center. After administration of the racemate, the results indicated the differences in plasma concentrations and pharmacokinetic parameters between enantiomers were stereoselctive. The metabolism might be mainly responsible for the chiral pharmacikinetics of the enantiomers. The quantitation of enantiomers in biological matrix was based on the development of chiral separation techniques. In this paper, the chiral separation techniques of these agents and the advance in chiral pharmacokinetics of ketoconazole and itraconazole were reviewed, which could provide some references to the discovery of azole antifungal new agents.
- antifungal drugs /
- chiral separation /
- pharmacokinetics /
- stereo selectivity

[1]	姚彤炜. 手性药物分析 [M].北京:人民卫生出版社, 2008:9.
[2]	Williams ML, Wainer IW. Role of chiral chromatography in therapeutic drug monitoring and in clinical and forensic toxicology[J]. Ther Drug Monit, 2002, 24(2):290.
[3]	Soudijn W, Van Wijngaarden I, Ijzerman AP. Stereoselectivity of drug-receptor interactions[J].Drugs, 2003, 6(1):43.
[4]	黄晓龙. 浅谈在立体异构体新药研究中需注意的问题[J]. 中国新药杂志, 2001, 10(1):65.
[5]	黄晓龙. 美国FDA关于开发立体异构体新药的政策简介[J].中国新药杂志, 2000, 9(9):650.
[6]	Wang X, Zeng S. Stereoselective metabolic and pharmacokinetic analysis of the chiral active components from herbal medicines[J]. Curr Pharm Anal, 2010, 6(1):39.
[7]	盛春泉, 张万年, 季海涛, 等. 抗真菌药物的创新设计研究[J]. 中国新药杂志, 2004, 13(2):97.
[8]	朱静. 伏立康唑的药理特性及临床应用[J]. 天津药学, 2007, 19(4):48.
[9]	Ekiert RJ, Krzek J, Talik P. Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review[J]. Talanta,2010, 82(4):1090.
[10]	Hassan YA, Imran A. Comparative study of the enantiomeric resolution of chiral antifungal drugs econazole, miconazole and sulconazole by HPLC on various cellulose chiral columns in normal phase mode[J]. J Pharm Biomed Anal, 2002, 27(3-4):441.
[11]	汪永忠. 伏立康唑对映体的手性高效液相色谱分离[J]. 中国药师, 2006, 9(3):231.
[12]	刘爱, 葛文娜, 吴淑燕, 等. 手性流动相添加法拆分酮康唑外消旋体[J]. 色谱, 2009, 27(2):240.
[13]	Hamdy DA, Brocks DR. A stereospecific high-performance liquid chromatographic assay for the determination of ketoconazole enantiomers in rat plasma[J]. Biomed Chromatogr, 2008, 22(5):542.
[14]	陈伟成, 刘长海, 张海, 等. 毛细管电泳手性拆分方法的研发策略[J]. 药学实践杂志, 2010, 28(2):130.
[15]	侯莹, 纪松岗, 赵亮, 等. 毛细管区带电泳对5种三唑类化合物的手性分离[J]. 药学实践杂志, 2008, 26(3):214.
[16]	Castro-Puyana M, Crego AL, Marina ML. Enantiomeric separation of ketoconazole and terconazole antifungals by electrokinetic chromatography:Rapid quantitative analysis of ketoconazole in pharmaceutical formulations[J]. Electrophoresis, 2005, 26(20):3960.
[17]	Castro-Puyana M, Crego AL, Marina ML. Separation and quantitation of the four stereoisomers of itraconazole in pharmaceutical formulations by electrokinetic chromatography[J]. Electrophoresis, 2006, 27(4):887.
[18]	李关宾, 林秀丽, 蒋文强, 等. 胶束电动毛细管色谱法分离酮康唑手性异构体[J]. 分析化学, 2000, 28(5):653.
[19]	Hermawan D, Ibrahim WAW, Sanagi MM, et al. Chiral separation of econazole using micellar electrokinetic chromatography with hydroxypropyl-γ-cyclodextrin[J]. J Pharm Biomed Anal, 2010, 53(5):1244.
[20]	Castro-Puyana M, Crego AL, Marina ML, et al. Enantioselective separation of azole compounds by EKC. Reversal of migration order of enantiomers with CD concentration[J]. Electrophoresis, 2007,28(15):2667.
[21]	Breadmore MC, Thormann W. Capillary electrophoresis evidence for the stereoselective metabolism of itraconazole in man[J]. Electrophoresis, 2003, 24(15):2588.
[22]	Hamdy DA, Brocks DR. Nonlinear stereoselective pharmacokinetics of ketoconazole in rat after administration of racemate[J]. Chirality, 2009, 21(7):704.
[23]	Dilmaghanian S, Gerber JG, Filler SG, et al. Enantioselectivity of inhibition of cytochrome P450 3A4 (CYP3A4) by ketoconazole:testosterone and methadone as substrates[J]. Chirality, 2004, 16(2):79.
[24]	Kunze KL, Nelson WL, Kharasch ED, et al. Stereochemical aspects of itraconazole metabolism in vitro and in vivo[J]. Drug Metab Dispos, 2006, 34(4):583.

[1]	张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英. 二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(): 1-6. doi: 10.12206/j.issn.2097-2024.202308062
[2]	骆锦前, 王婷, 尤本明, 陈方剑. 姜黄素纳米乳的制备和药动学及药效学研究 . 药学实践与服务, 2023, 41(7): 416-421, 436. doi: 10.12206/j.issn.2097-2024.202209084
[3]	何晓波, 朱佳慧, 高方圆. 生物技术药物药代动力学研究进展 . 药学实践与服务, 2019, 37(5): 394-399. doi: 10.3969/j.issn.1006-0111.2019.05.003
[4]	王韵, 柴逸峰, 朱臻宇. 基于疾病动物模型的中药药动学研究进展 . 药学实践与服务, 2017, 35(2): 108-111,140. doi: 10.3969/j.issn.1006-0111.2017.02.003
[5]	白国静, 边晓杰, 姚阔, 吴俊琪, 俞世冲, 孟庆国, 吴秋业. 肿瘤相关糖抗原GM3及其衍生物合成方法研究进展 . 药学实践与服务, 2016, 34(1): 5-7,15. doi: 10.3969/j.issn.1006-0111.2016.01.002
[6]	恽芸蕾, 高守红, 樊成辉, 缪海均. 米格列奈钙片健康人体药动学研究 . 药学实践与服务, 2014, 32(1): 45-48. doi: 10.3969/j.issn.1006-0111.2014.01.011
[7]	姚亚敏, 沐俊, 孙骥, 马芳, 卢洪洲, 张丽军. 洛匹那韦药代动力学的研究进展 . 药学实践与服务, 2012, 30(5): 336-339. doi: 10.3969/j.issn.1006-0111.2012.05.005
[8]	高守红, 温燕, 邬蓉, 金晓玲, 恽芸蕾, 李静娴, 缪海均. 注射用盐酸米诺环素在健康人体的药物动力学 . 药学实践与服务, 2009, 27(3): 193-194,200.
[9]	孔令媛, 马骏. 液相色谱法测定羟基喜树碱含量及药动学研究 . 药学实践与服务, 2007, (6): 379-381.
[10]	王佩贤, 曹永孝, 杨孝江, 姚鸿萍, 王秀芹. 注射用复方氨苄西林钠药代动力学研究 . 药学实践与服务, 2007, (1): 18-20,30.
[11]	吕竹芬, 谢清春, 陈燕忠, 申楼, 周松. 西替伪麻缓释片中盐酸伪麻黄碱的动物药代动力学研究 . 药学实践与服务, 2006, (6): 342-345.
[12]	刘新宇, 吴芳. 头孢丙烯在下呼吸道细菌感染患者的药代动力学研究 . 药学实践与服务, 2006, (3): 144-146.
[13]	江力宣, 闫海英, 阳盛洪, 邱旭民. 药代动力学研究在新药研发中的应用 . 药学实践与服务, 2006, (5): 260-263,288.
[14]	樊蓉, 张纯, 高申. 蛋白多肽类药物的药代动力学研究概况 . 药学实践与服务, 2006, (3): 135-138.
[15]	刘新宇, 吴芳, 陈连剑. 单剂量口服茶碱缓释胶囊的人体生物等效性评价 . 药学实践与服务, 2001, (3): 146-148.
[16]	田四琦, 刘会臣. 手性药物对映体药效学的立体选择性 . 药学实践与服务, 1999, (6): 346-348.
[17]	陆文铨, 罗新庚, 朱文娟. 复方新诺明和甲氧等氨嘧啶对丁胺卡那霉素药代动力学的影响 . 药学实践与服务, 1997, (5): 259-264.
[18]	尹玉琴, 陈振德, 蒋世新. 布美他尼与地高辛相互作用及药代动力学考察 . 药学实践与服务, 1997, (4): 224-225.
[19]	丁惠萍, 黄平. 抗肿瘤药物的药代动力学及血浓度测定 . 药学实践与服务, 1996, (1): 37-40.
[20]	王睿, 孙效东, 段云鹏, 包尔宁, 陆茵. 哌拉西林在胆道手术患者中的药代动力学研究 . 药学实践与服务, 1994, (3): 5-10.

点击查看大图

计量

文章访问数: 4238
HTML全文浏览量: 294
PDF下载量: 1727
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

唑类抗真菌药物手性分离及药代动力学研究进展

doi: 10.3969/j.issn.1006-0111.2012.06.006

Advance in chiral separation and stereo selectivity pharmacokinetics of azole antifungal drugs

计量

唑类抗真菌药物手性分离及药代动力学研究进展

doi: 10.3969/j.issn.1006-0111.2012.06.006

English Abstract

Advance in chiral separation and stereo selectivity pharmacokinetics of azole antifungal drugs

全文HTML

目录

留言板

唑类抗真菌药物手性分离及药代动力学研究进展

doi: 10.3969/j.issn.1006-0111.2012.06.006

Advance in chiral separation and stereo selectivity pharmacokinetics of azole antifungal drugs

计量

出版历程

唑类抗真菌药物手性分离及药代动力学研究进展

doi: 10.3969/j.issn.1006-0111.2012.06.006

English Abstract

Advance in chiral separation and stereo selectivity pharmacokinetics of azole antifungal drugs

全文HTML

目录