Study of the Pharmacokinetics, Tolerability, and Safety of Fixed-Dose Combinations of Gramicidin S and Cetylpyridinium Chloride

The aim of the study was to compare the safety, tolerability, and pharmacokinetic profile of Grammidin® neo, lozenges, and Grammidin®, a metered-dose topical spray, manufactured by Valenta Pharm JSC, Russia, following single-dose administration in healthy volunteers. Material and methods. An open-label, randomized, two-period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic parameters of Grammidin® (metered-dose topical spray) compared to Grammidin® neo (lozenges). Healthy volunteers were randomized into two sequence groups according to the order of drug administration in periods I and II of the study. In group 1, subjects received 1 lozenge of Grammidin® neo during period I. In period II, the same volunteers received 4 sprays of Grammidin® to the oral and pharyngeal mucosa applied by the researcher. Group 2 subjects received the study medications in reverse order. The washout period between administrations of the study drugs was 7 days. Concentrations of the active pharmaceutical substances were determined in plasma using high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) with prior analyte extraction from the biological matrix. The study included ongoing monitoring of vital signs, as well as assessments of laboratory parameters (complete blood count, serum biochemistry, and urinalysis) and standard 12-lead ECG recordings. All subject-reported complaints, as well as any abnormalities or clinically significant deviations from reference ranges in general health status, laboratory findings, or ECG parameters were documented and categorized by the researcher as adverse events (AEs). Results. Of the 16 volunteers who received the study drugs in periods I and II, only 6 demonstrated plasma concentrations of gramicidin S and cetylpyridinium chloride above the lower limit of quantification (LLOQ) at isolated time points. Due to the insufficient number of measurable concentrations, pharmacokinetic parameters could not be reliably calculated. During the study, one mild adverse event (AE) was reported in a single volunteer — pain at the catheter insertion site. The relationship between this AE and study drug administration was assessed by the researcher as indeterminate. This AE resolved spontaneously without any therapeutic intervention. Conclusion. Topical administration of gramicidin S and cetylpyridinium chloride to the oropharyngeal mucosa resulted in minimal systemic exposure, making pharmacokinetic characterization unfeasible. The fixed-dose combination was safe and well tolerated in all participants, with no meaningful differences observed between the lozenge and spray formulations.

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