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

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 IC 50 values of 3873 and 3722 µmol/L, respectively. Secnidazole did not exhibit time‐dependent inhibition. There was no inhibition (IC 50 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.

Efficacy and Safety of Single Oral Dosing of Secnidazole for Trichomoniasis in Women: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Delayed-Treatment Study

“…In our study, 2.7% of patients reported nausea with SEC. Additionally, SEC does not have an alcohol restriction based on data from in vitro studies [ 13 , 14 ].…”

“…Patients were counseled to notify all sexual partners within the past 60 days to be treated as contacts to trichomoniasis. Based on data from in vitro studies [ 13 ], and as noted in the package insert [ 14 ], SEC does not have an alcohol consumption restriction. Patients were excluded if they were pregnant (owing to placebo-controlled study design) or lactating, had symptomatic vulvovaginal candidiasis or an active genital herpes outbreak, received a course of antibacterial or antifungal therapy within the past 14 days, or had a known allergy to nitroimidazoles.…”