ROLE OF THE RED BLOOD-CELL IN DRUG-METABOLISM
ROLE OF THE RED BLOOD-CELL IN DRUG-METABOLISM
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DOI：
10.1002/bod.2510090402
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发表时间：
1988-07-01
影响因子：
2.1
通讯作者：
COSSUM, PA
中科院分区：
文献类型：
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作者：
COSSUM, PA
与认为红细胞对药理活性的内源性和外源性物质没有代谢活性相反，很明显，除了催化一系列药物的各种其他转化的能力外，红细胞还具有中等的细胞色素P-450样活性。有证据表明红细胞代谢的药物清单(表1)包含几种药物类别的例子。然而，一些主要通过新陈代谢在体内清除的主要药物类别缺失(例如，苯二氮卓类药物)。此外，目前还没有证据表明红细胞有能力进行更重要的药物结合反应(葡萄糖醛酸化、硫化)，尽管有证据表明存在其他结合反应(甲基化、乙酰化、谷胱甘肽结合)。可以想象，红细胞可以作为一种方便的组织，添加到药物开发中使用的其他代谢筛选程序中。红细胞已被用于鉴定快乙酰化和慢乙酰化。其他人则使用红细胞来确定药物代谢中可能存在的性别差异。希望这篇综述激发了人们对红细胞代谢药物能力的兴趣，这种兴趣将导致进一步的发现。
Contrary to the belief that the RBC is not metabolically active towards pharmacologically active endogenous and exogenous substances, it is evident that the RBC contains moderate cytochrome P-450-like activity, in addition to the ability to catalyse various other transformations of a range of drugs. The list of drugs for which there is evidence of metabolism by RBC (Table 1) contains examples from several drug classes. However some major classes of drugs which are principally cleared in vivo by metabolism are missing (for example, benzodiazepines). Moreover, there is as yet no evidence for the RBC having the capacity for the more important drug conjugation reactions (glucuronidation, sulphation) although there is evidence of other conjugation reactions (methylation, acetylation, glutathione conjugation). It is conceivable that the RBC could be used as a convenient tissue to add to other metabolism screening procedures used in drug development. Already use has been made of the RBC in identifying fast and slow acetylators. Others have used RBC to identify a possible sex-based difference in drug metabolism. Hopefully, this review has stimulated interest in the ability of the RBC to metabolize drugs and this interest will result in further discoveries.