A single-dose oral granule formulation of secnidazole 2 g (SOLOSEC ) has been approved in the US as a treatment for bacterial vaginosis. Available data on the likelihood of in vitro drug-drug and alcohol-drug interactions are limited. Secnidazole was incubated with cultured human hepatocytes over a range of concentrations (0-10 000 μmol/L) to assess metabolic profiling. Cytochrome P450 (CYP) and aldehyde dehydrogenase inhibition over a similar concentration range were evaluated in human liver microsomes (HLMs) or recombinant enzymes using competition or time-dependent inactivation assays. Secnidazole exhibited very low metabolism in HLMs at concentrations up to 6400 µmol/L. Secnidazole was found to be metabolized to a limited extent predominantly by CYP3A4 and CYP3A5 among a panel of cDNA-expressed enzymes. Secnidazole inhibited CYP2C19 and CYP3A4, with IC values of 3873 and 3722 µmol/L, respectively. Secnidazole did not exhibit time-dependent inhibition. There was no inhibition (IC value >5000 µmol/L) observed for any other CYP enzyme or with human recombinant aldehyde dehydrogenase 2 (ALDH2). These results are the first reported observation of the metabolism and drug-drug interaction profile for secnidazole and demonstrate that the agent has minimal to no potential drug interactions of concern.
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| http://dx.doi.org/10.1002/prp2.634 | DOI Listing |
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