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

GUO Kai-xin; SHI Kuan; WEN Jun; ZHOU Ting-ting; FAN Guo-rong

doi:10.3969/j.issn.1006-0111.2012.06.006

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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.

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

Received Date: 2011-05-11

Rev Recd Date: 2011-10-13

Key words:

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.

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Reference (24)

[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.

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

doi: 10.3969/j.issn.1006-0111.2012.06.006

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