The clinically useful optimum dose of
omoconazole nitrate, a topical
antifungal agent, has been examined by analysing the percutaneous pharmacokinetics of the
drug to assess its pharmacological activity in an in-vivo study. Creams containing
omoconazole nitrate were prepared on a pilot basis. The
therapeutic effect of the
omoconazole nitrate creams was examined in an in-vivo pharmacological
dermatophytosis infection model in guinea-pigs. Creams containing 0.25% or higher concentrations of
omoconazole nitrate resulted in significant inhibition compared with no treatment and with vehicle-treated controls. In the mycological examination no growth of dermatophytes was observed for creams containing 1% or higher concentrations. In an in-vitro hairless mouse skin-permeability test a non-linear least squares program based on a fast inverse Laplace transform algorithm was used to calculate the partition and diffusion parameters of
omoconazole nitrate in the stratum corneum and viable epidermis. The time-course of
drug concentrations in the skin of the guinea-pig, estimated on the basis of these parameters, led to predictions that percutaneous
drug concentrations on the guinea-pig would require 10 or more days to reach equilibrium in the skin; that
drug concentrations in the corneum-viable epidermis border, where dermatophytes are considered to grow, would exceed the minimum effective concentration when 0.1% higher concentration creams were used; and that for binding to
keratin drug concentrations would reach the practical minimum effective concentration when creams containing 0.5% or more
omoconazole nitrate were used. These results show that partition and diffusion parameters obtained from in-vitro skin permeation studies can be used to predict in-vivo percutaneous pharmacokinetics and to estimate therapeutically effective concentrations.