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

• Main Authors: Helen S. Pentikis (Author), Nikki Adetoro (Author), Gregory Kaufman (Author)
• Format: Book
• Published: Wiley, 2020-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2052-1707; 10.1002/prp2.634
• Keywords: antibiotic; bacterial vaginosis; secnidazole; Therapeutics. Pharmacology; RM1-950
• Source: Pharmacology Research & Perspectives, Vol 8, Iss 4, Pp n/a-n/a (2020)

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.