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药物性间质性肺病与细胞色素 P450 多态性的关系。

Relationship between drug-induced interstitial lung diseases and cytochrome P450 polymorphisms.

机构信息

Department of Clinical Chemistry, ild care center, Maastricht University Medical Centre, Maastricht, The Netherlands.

出版信息

Curr Opin Pulm Med. 2010 Sep;16(5):496-502. doi: 10.1097/MCP.0b013e32833c06f1.

Abstract

PURPOSE OF REVIEW

Interstitial lung disease and especially drug-induced interstitial lung disease can occur as a cause of drug(s) or drug-drug interactions. In this review we summarize the possible role of cytochrome P450 (CYP) enzymes in drug-induced interstitial lung disease.

RECENT FINDINGS

The CYP enzyme family plays an important role in the metabolism of all sorts of ingested, injected or inhaled xenobiotic substances. Although the liver is considered to be the major metabolism site of CYP enzymes, in recent years more CYP isoforms have been detected in lung tissue. Polymorphisms in these CYP genes can influence the metabolic activity of the subsequent enzymes, which in turn may lead to localized (toxic) reactions and tissue damage.

SUMMARY

Drug toxicity can be the consequence of no or very poor enzyme activity, especially if no other metabolic route is available. In the case of reduced enzyme activity, dose reduction or prescribing an alternative drug metabolized by a different, unaffected CYP enzyme is recommended to prevent toxic side effects. Therefore, knowing a patient's CYP profile before drug prescription could be a way to prevent drug-induced interstitial lung disease. Moreover, it might be helpful in explaining serious adverse effects from inhaled, injected or ingested xenobiotic substances.

摘要

目的综述

间质性肺疾病,尤其是药物性间质性肺疾病,可能是药物或药物相互作用引起的。在这篇综述中,我们总结了细胞色素 P450(CYP)酶在药物性间质性肺疾病中的可能作用。

最近的发现

CYP 酶家族在各种摄入、注射或吸入的外源物质的代谢中起着重要作用。虽然肝脏被认为是 CYP 酶的主要代谢部位,但近年来在肺组织中发现了更多的 CYP 同工酶。这些 CYP 基因的多态性可影响后续酶的代谢活性,从而可能导致局部(毒性)反应和组织损伤。

总结

药物毒性可能是由于缺乏或非常低的酶活性所致,特别是如果没有其他代谢途径可用的话。在酶活性降低的情况下,建议减少剂量或开一种由不同的、未受影响的 CYP 酶代谢的替代药物,以防止毒性副作用。因此,在开处方前了解患者的 CYP 谱可能是预防药物性间质性肺疾病的一种方法。此外,它可能有助于解释吸入、注射或摄入的外源物质的严重不良反应。

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