Rozex Mechanism of Action

Pharmacology: Pharmacodynamics: Metronidazole has an antibacterial and antiprotozoal effect against a large number of pathogenic microorganisms. The mechanism of action of metronidazole in rosacea is not known but pharmacological data available suggest that the activity is based on an antibacterial and/or anti-inflammatory action.
Pharmacokinetics: Following a single, topical 7.5mg application of ROZEX Gel to the face of ten rosacea patients (aged 36 to 70 years), the maximum metronidazole serum concentration (C_max) ranged from below detectable limits (n=3) to 66 ng/mL, with a mean in the seven patients with quantifiable serum concentrations of 40.6 ng/mL. The mean C_max following 30 mg oral dose of a 5 mg/mL metronidazole solution administered in the same patients was 850 ng/mL. When corrected for the dose difference between formulations, the estimated C_max for the oral solution is 212 ng/mL. The difference in C_max between the two formulations was significant (p < 0.01). The time of the maximum serum concentration (T_max) was also found to be significantly (p < 0.01) different between the two formulations. The median T_max was 5.98 hours with the topical gel as compared to 0.97 hours with the oral solution. An accurate estimation of the area under the curve (AUC) following the topical 0.75% gel was not possible because of undetectable serum concentrations at the majority time points. The mean (%CV) AUC following the oral solution was 7476.1 (35.8%) ng·hr/mL. Serum metronidazole and the hydroxymethyl metabolite (2-hydroxymethylmetronidazole) were below the detectable limits of the assay (< 25 ng/mL) at the majority of time points in all patients after topical administration.
Toxicology: Carcinogenesis: Tumorigenicity in Rodents: Metronidazole has shown evidence of carcinogenic activity in a number of studies involving chronic, oral administration in mice and rats but not in studies involving hamsters. These studies have not been conducted with 0.75% metronidazole gel which would result in significantly lower systemic blood levels than oral formulations.
Mutagenicity Studies: Although metronidazole has shown mutagenic activity in a number of in vitro bacterial assay systems, studies in mammals (in vivo) have failed to demonstrate a potential for genetic damage.