In-vitro permeability of the human nail and of a keratin membrane from bovine hooves: prediction of the penetration rate of antimycotics through the nail plate and their efficacy.
In contrast to the partition coefficient octanol/water the molecular size of penetrating drugs has a noticeable influence on the permeability of the human nail plate and a keratin membrane from bovine hooves. The relationship between permeability and molecular weight is founded on well-established theories. The correlation between the permeability of the nail plate and that of the hoof membrane allows a prediction of the nail permeability after determination of the drug penetration through the hoof membrane. The maximum flux of ten antimycotics (amorolfine, bifonazole, ciclopirox, clotrimazole, econazole, griseofulvin, ketoconazole, naftifine, nystatin and tolnaftate) through the nail plate was predicted on the basis of their penetration rates through the hoof membrane and their water solubilities. An efficacy coefficient against onychomycoses was calculated from the maximum flux and the minimum inhibitory concentration. Accordingly, amorolfine, ciclopirox, econazole and naftifine are expected to be especially effective against dermatophytes, whereas in the case of an infection with yeasts only, amorolfine and ciclopirox are promising.
Mertin
D
D
Department of Pharmaceutical Technology, Heinrich-Heine-University, Düsseldorf, Germany.
Lippold
B C
BC
D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability; D006724:Hoof and Claw / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007633:Keratins / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D009262:Nails / Q000378:metabolism*; D010539:Permeability
D000935:Antifungal Agents; D007633:Keratins