1. Academic Validation
  2. In vitro metabolic profile and drug-drug interaction assessment of secnidazole, a high-dose 5-nitroimidazole antibiotic for the treatment of bacterial vaginosis

In vitro metabolic profile and drug-drug interaction assessment of secnidazole, a high-dose 5-nitroimidazole antibiotic for the treatment of bacterial vaginosis

  • Pharmacol Res Perspect. 2020 Aug;8(4):e00634. doi: 10.1002/prp2.634.
Helen S Pentikis 1 Nikki Adetoro 2 Gregory Kaufman 2
Affiliations

Affiliations

  • 1 SAJE Consulting, Baltimore, MD, USA.
  • 2 Lupin Pharmaceuticals, Baltimore, MD, USA.
Abstract

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 IC50 values of 3873 and 3722 µmol/L, respectively. Secnidazole did not exhibit time-dependent inhibition. There was no inhibition (IC50 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.

Keywords

antibiotic; bacterial vaginosis; secnidazole.

Figures
Products