Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: other dermatics, wart product and keratolytic treatment ATC code: D11AF

Mechanism of action of fluorouracil

The active ingredient fluorouracil (FU) belongs to the cytostatics that act as anti-metabolites.
As a result of its structural similarity with to Thymine (5-Methyluracil), which is present in nucleinic acids, FU prevents formation and use of this and in this way inhibits both DNA and RNA synthesis.
Consequently the growth of the wart virus is inhibited resulting in the inhibited growth of the kinds of cells in particular which are in the accelerated growth stage, as with warts, and therefore absorb FU in increased amounts.
Thymine Fluorouracil

Mechanism of action of salicylic acid

Salicylic acid was added because of its keratolytic properties, to facilitate penetration of the active ingredient, which is especially difficult in warts. The same is achieved by the solubilizing agent for the active ingredient FU, dimethyl sulfoxide. The keratolytic action of salicylic acid is based on direct effect on the intercellular glue substances or desmosomes promoting the keratinization process.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties

In a resorption study on pigs it could be proved that there was no fluorouracil in the serum after the cutaneous application, even in large amounts of Verrumal Solution i.e. the active ingredient was not resorbed in an amount that could be detected using standard analytical methods (HPLC).

According to more recent analysis, the fluorouracil resorption rate in people after use of Verrumal Solution is significantly less than 0.1 %.

After application on the skin, Verrumal Solution forms a strong white looking film on the skin once the solution has evaporated. Thus, an occlusive effect is achieved to benefit the difficult penetration of the active ingredient particularly with warts.

Animal experiments and human pharmacokinetic studies show that salicylic acid penetrates quickly depending on the basis and penetration influencing factors, such as skin condition.

Salicylic acid is metabolized by the conjugation with glycine into salicyluric acid, with gluconic acid from the phenolic OH group into ether glucuronide and on the COOH group into ester glucuronide, while via hydroxylation it is metabolized into gentisic or dihydroxybenzoic acid. The half-life of systemically resorbed salicylic acid is between 2 and 3 hours in the normal dose range and can increase to 15 to 30 hours with high posology as a consequence of the liver's limited capacity to conjugate salicylic acid.

With a topical application of salicylic acid, no toxic undesirable effects are generally expected (if all contraindications are observed!) as a serum level over 5 mg/ml can barely be reached. Early symptoms of salicylate intoxication can only occur with serum levels over 30 mg/dl.