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Chem Res Toxicol. 2014 Nov 17;27(11):1967-71. doi: 10.1021/tx5003113. Epub 2014 Oct 13.

Human sulfotransferase 1A1-dependent mutagenicity of 12-hydroxy-nevirapine: the missing link?

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Department of Genetics/CIGMH, NOVA Medical School/Faculdade Ciências Médicas, Universidade Nova de Lisboa , Rua da Junqueira 100, 1349-008 Lisbon, Portugal.


Nevirapine (NVP) is a frequently used anti-HIV drug. Despite its efficacy, NVP has been associated with serious skin and liver injuries in exposed patients and with increased incidences of hepatoneoplasias in rodents. Current evidence supports the involvement of reactive metabolites in the skin and liver toxicities of NVP, formed by cytochrome P450-mediated oxidations and/or subsequent phase II sulfonation. However, to date, standard in vitro genotoxicity tests have provided no evidence that NVP is either mutagenic or clastogenic. The human sulfotransferase 1A1-dependent mutagenicity of 12-hydroxy-NVP, one of the major metabolites of NVP, is demonstrated here.

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