Chlorhexidine Gluconate 1% w/w, Lignocaine 2% w/w, Metronidazole 1% w/w Topical gel

The mechanism of action of metronidazole in the treatment of rosacea is unknown.

Topical administration of a one-gram dose of metronidazole gel to the face of 13 subjects with moderate to severe rosacea once daily for 7 days resulted in a mean ± SD C maxof metronidazole of 32 ± 9 ng/mL. The mean ± SD AUC (0-24)was 595 ± 154 ng*hr/mL. The mean C maxand AUC (0-24)are less than 1% of the value reported for a single 250 mg oral dose of metronidazole. The time to maximum plasma concentration (T max) was 6 to 10 hours after topical application.

Lidocaine HCl stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.

Lidocaine HCl may be absorbed following topical administration to mucous membranes, its rate of absorption and percent of dose absorbed depending upon concentration and total dose administered, the specific site of application and duration of exposure. In general, the rate of absorption of local anesthetic agents following topical application occurs most rapidly after intratracheal administration. Lidocaine HCl is well-absorbed from the gastrointestinal tract, but little intact drug appears in the circulation because of biotransformation in the liver.

Lidocaine HCl is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidney. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine HCl. Approximately 90% of lidocaine HCl administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.

The plasma binding of lidocaine HCl is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL, 60 to 80 percent of lidocaine HCl is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Lidocaine HCl crosses the blood-brain and placental barriers, presumably by passive diffusion.

Studies of lidocaine HCl metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. Because of the rapid rate at which lidocaine HCl is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine HCl kinetics but may increase the accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine HCl required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg free base per mL. In the rhesus monkey arterial blood levels of 18 to 21 mcg/mL have been shown to be threshold for convulsive activity.