对映异构体与外消旋混合物的安全性特征：它们一样吗？

Safety profile of enantiomers vs. racemic mixtures: it's the same?

机构信息

Service de Pharmacologie Clinique, Equipe de Pharmacoépidémiologie, INSERM U 1027, Université de Toulouse, Faculté de Médecine, 37 allées Jules Guesde, Toulouse, France.

出版信息

Br J Clin Pharmacol. 2012 Nov;74(5):886-9. doi: 10.1111/j.1365-2125.2012.04262.x.

DOI:10.1111/j.1365-2125.2012.04262.x

PMID:22404187

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3495153/

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

The physicochemical properties of racemates and stereoisomers of medicines can differ significantly, and this may affect the side-effect profile in addition to the pharmacokinetics and intended pharmacology.

WHAT THIS STUDY ADDS

This is a study to investigate the profile of adverse drug reactions of racemic and enantiomeric forms of drugs. Our data suggest differences in the safety profile for ofloxacin and omeprazole. This area requires more work to investigate this for other compounds.

AIMS

The objective was to investigate the safety profile of four drugs marketed as racemic and enantiomeric forms in France.

METHODS

Data from the French PharmacoVigilance Data Base (January 2005 to June 2010) were analysed for four pairs of racemic/isomeric drugs. A case-noncase approach was used to measure the disproportionality of combination between adverse drug reaction (ADR) and exposure to drug.

RESULTS

No significant difference in the number of ADRs was observed between Rac-cetirizine/(R)-cetirizine or Rac-citalopram/(S)-citalopram pairs. (S)-Omeprazole induced more haematological effects than Rac-omeprazole. Rac-Ofloxacin induced more haematological, renal and neuropsychiatric ADRs than (S)-ofloxacin, whereas levofloxacin was associated with more reports of musculoskeletal ADRs.

CONCLUSIONS

The profile of ADRs could differ for some drugs marketed as racemic and enantiomeric forms. Further studies would be necessary to confirm these data.

摘要

已知本课题的相关信息

药物的外消旋体和立体异构体的物理化学性质可能存在显著差异，除了药代动力学和预期的药理学之外，这还可能影响副作用的发生情况。

本研究的新增内容

本研究旨在调查外消旋体和对映异构体药物的不良反应发生情况。我们的数据表明氧氟沙星和奥美拉唑的安全性特征存在差异。该领域需要进一步研究其他化合物的情况。

目的

目的是研究法国上市的四种作为外消旋体和对映异构体的药物的安全性特征。

方法

使用病例对照方法分析了法国药物警戒数据库（2005 年 1 月至 2010 年 6 月）中的四组外消旋/对映异构体药物的数据。用以评估不良反应（ADR）与药物暴露之间的组合是否不成比例。

结果

未观察到 R-西替利嗪/（R）-西替利嗪或 R-西酞普兰/（S）-西酞普兰这两种外消旋体药物组合的不良反应数量存在显著差异。（S）-奥美拉唑比 rac-奥美拉唑引起更多的血液学效应。Rac-氧氟沙星比（S）-氧氟沙星引起更多的血液学、肾脏和神经精神方面的不良反应，而左氧氟沙星则与更多的肌肉骨骼不良反应报告相关。