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Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions.

2014Journal article Open access
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dc.contributor.authorMarinho, A
dc.contributor.authorRodrigues, P
dc.contributor.authorCaixas, U
dc.contributor.authorAntunes, A
dc.contributor.authorBranco, T
dc.contributor.authorHargivan, S
dc.contributor.authorMarques, M
dc.contributor.authorMonteiro, E
dc.contributor.authorPereira, S
dc.date.accessioned2015-08-13T14:00:41Z
dc.date.available2015-08-13T14:00:41Z
dc.date.issued2014
dc.description.abstractOBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.por
dc.identifier.citationJ Antimicrob Chemother. 2014 Feb;69(2):476-82por
dc.identifier.doi10.1093/jac/dkt359
dc.identifier.urihttp://hdl.handle.net/10400.10/1481
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherBritish Society for Antimicrobial Chemotherapypor
dc.relation.publisherversionhttp://jac.oxfordjournals.org/content/69/2/476.full.pdf+htmlpor
dc.subjectNevirapinepor
dc.subjectAnti-HIV agentspor
dc.subjectDrug-related side effects and adverse reactionspor
dc.subjectAdverse drug reactionspor
dc.titleDifferences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions.por
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceLondonpor
oaire.citation.endPage482por
oaire.citation.startPage476por
oaire.citation.titlehe Journal of antimicrobial chemotherapy.por
oaire.citation.volume69por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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