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On Mechanisms of Reactive Metabolite Formation from Drugs
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.ORCID-id: 0000-0002-8083-2864
2013 (engelsk)Inngår i: Mini-Reviews in medical chemistry, ISSN 1389-5575, E-ISSN 1875-5607, Vol. 13, nr 5, s. 720-729Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Idiosyncratic adverse drug reactions (IADRs) cause a broad range of clinically severe conditions of which drug induced liver injury (DILI) in particular is one of the most frequent causes of safety-related drug withdrawals. The underlying cause is almost invariably formation of reactive metabolites (RM) which by attacking macromolecules induce organ injuries. Attempts are being made in the pharmaceutical industry to lower the risk of selecting unfit compounds as clinical candidates. Approaches vary but do not seem to be overly successful at the initial design/synthesis stage. We review here the most frequent categories of mechanisms for RM formation and propose that many cases of RMs encountered within early ADME screening can be foreseen by applying chemical and metabolic knowledge. We also mention a web tool, SpotRM, which can be used for efficient look-up and learning about drugs that have recognized IADRs likely caused by RM formation.

sted, utgiver, år, opplag, sider
2013. Vol. 13, nr 5, s. 720-729
Emneord [en]
Reactive metabolite, drug safety, hepatotoxicity, idiosyncratic adverse drug reaction, web application, structural alerts, bioactivation
HSV kategori
Forskningsprogram
Bioinformatik; Läkemedelsmetabolism
Identifikatorer
URN: urn:nbn:se:uu:diva-183848DOI: 10.2174/1389557511313050009ISI: 000317271100009PubMedID: 23035789OAI: oai:DiVA.org:uu-183848DiVA, id: diva2:564769
Tilgjengelig fra: 2012-11-04 Laget: 2012-11-04 Sist oppdatert: 2017-12-07bibliografisk kontrollert

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Forlagets fulltekstPubMedhttp://www.eurekaselect.com/108113/article

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