Difference in Percutaneous Absorption and Intracutaneous Distribution in Guinea Pigs among Topical Antifungal Drugs (Tioconazole Solution, Tioconazole Cream, Miconazole Nitrate Solution and Bifonazole Solution)

Abstract

Tioconazole (TCZ) is an imidazole antifungal agent with broad spectrum activity in vitro against dermatophytes and yeasts, as well as against some chlamydia, trichomonads and Gram-positive bacteria.1,2) Its in vitro antifungal activity against dermatophytes, yeasts and bacteria is equal or stronger in comparison with those of the known imidazoles, miconazole nitrate (MCZ), bifonazole (BFZ) and clotrimazole. [3][4][5] TCZ has a dual mechanism of antifungal action that is inhibition of sterol biosynthesis and direct cell membrane damage. [6][7][8] In growing cultures, TCZ exerts a potent killing action. The extent and rapidity of this fungicidal effect of TCZ are greater than those of MCZ and clotrimazole. 9,10) This activity is paralleled by good topical efficacy in a guinea pig dermatomycosis model. 2,9) At the beginning, TCZ was been used as a cream formulation. Clinical trials for treating superficial dermatophyte or yeast infections of the skin have clearly demonstrated once to three times a day topical applications of TCZ cream were at least as effective as alternative imidazole antifungal drugs, and in a few trials significantly greater efficacy has been reported for TCZ cream, compared with MCZ, clotrimazole, and econazole. 1,[11][12][13][14] After that TCZ solution was developed as over-the-counter drug. The efficacy and safety of twice or three times a day topical preparations of TCZ solution appear to be similar to those of TCZ cream and clotrimazole solution. [15][16][17][18] Pharmacokinetic studies in rats have demonstrated minimal systemic exposure following dermal application of TCZ cream.2) After a single application of TCZ cream about 16% of the applied radioactivity penetrates into rat skin and the percutaneous penetration into swine skin is considerably higher than that of clotrimazole cream.19) BFZ also penetrates far better into human skin than clotrimazole. 20) Clinical trials have clearly demonstrated the efficacy and safety of various formulations of BFZ applied once a daily in the treatment of superficial fungal infections of the skin.4) The skin retention time of MCZ in effective therapeutic concentrations is longer than that of BFZ. MCZ formulations are also recommended for once a daily application. 21) In the present study, in order to support the usefulness of once a daily applications of TCZ solution and cream, the percutaneous absorption and intracutaneous distribution of TCZ solution were investigated and compared with those of TCZ cream, MCZ solution and BFZ solution following a single topical application to abdominal skin of guinea pigs. (Tokyo, Japan). Itraconazole, IS for BFZ, was extracted from commercial preparations purchased from Janssen Kyowa Co., Ltd. (Tokyo, Japan). All other chemicals used were of reagent grade. MATERIALS AND METHODS MaterialsAnimals Guinea pigs of the Hartley strain (Japan SLC, Shizuoka, Japan) weighing approximately 400 g were used in the study. The animals were kept in an animal room main- Tioconazole (TCZ) is an imidazole antifungal agent with broa...

Perfil de suscetibilidade a antifúngicos de dermatófitos isolados de pacientes com insuficiência renal crônica

“…These results show that the fungicidal effect of tioconazole is greater than that of miconazole, as shown in the study by Sobue and Sekiguchi. 25 The mean geometric MFC values of ketoconazole, fluconazole and itraconazole confirm that high concentrations of these medications are required to obtain their fungistatic effect, according to the mechanism of azoles. 26 Furthermore, these results …”

Biopharmaceutical Development of a Bifonazole Multiple Emulsion for Enhanced Epidermal Delivery

“…Even in the lower layers of the epidermis, the BFZ accumulated is several times higher than the in vitro minimum inhibitory concentrations for dermatophytes, especially along the hair follicles as the preferred route of penetration [66]. This marked intracutaneous distribution has been described, for example, with tioconazole in guinea pig skin, detecting (after 2 h) around 300 µg/g in stratum corneum, but only 25 µg/g in epidermis [67]. These results confirm that if BFZ is relicted in the lipophilic skin regions then its apparent permeation through the dermis can be reduced dramatically [68,69] favoring its antifungal activity in the epidermic tissue.…”

Onychomycosis

“…It has been shown to have a broad spectrum of activity in vitro against dermatophytes and yeasts, as well as against some chlamydia, trichomonads, and Gram-positive bacteria. It inhibits ergosterol synthesis and additionally has a toxic effect on fungal cellular membrane (Sobue and Sekiguchi 2004 ). Complete cure rates after twice daily application of tioconazole 28 % nail solution for 48 weeks has been reported to be 22 % (Hay et al 1985 ).…”