Pharmacokinetics of cutaneous sulconazole nitrate in the hairless rat: absorption, excretion, tissue concentrations

Abstract

After cutaneous application of radioactive solutions of Sulconazole nitrate in the hairless rat, the total absorption of the substance by the skin, estimated from the sum of the cumulative urinary and fecal excretions over 96 h, was 2.4% of the dose administered. The elimination reached a maximum between 6 and 24 h and was virtually complete after 96 h. The excretion was almost equally distributed between the urine and the feces, which corresponds to an intense elimination via the biliary tract. The quantities present in the stratum corneum, epidermis and dermis at the end of the period of contact constituted another estimation of the total absorption of the substance which confirmed the previous estimation (3.6% of the dose). The measurement of the concentrations of Sulconazole and its metabolites in the various layers of the skin revealed a high affinity of the substance for the stratum corneum, where it remained present in large quantities for more than 48 h. This affinity is due to the very intense lipophilia of the molecule. The concentrations in the other tissues were inversely proportional to the distance from the surface of the skin and were virtually nil in the circulating blood. These results suggest the absence of risk of systemic effects after cutaneous administration of Sulconazole and support the recommended therapeutic protocol in man (one administration per day).

Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-κB and calcium activity repression

“…Furthermore, the effect of these drugs have been studied in the context of human pathologies treatment including cancer (13). Of these, SCZ is an antifungal agent with a broad spectrum of activity and is proposed for the treatment of skin infections such as dermatophyte infections (14)(15)(16). Compared to several imidazoles, SCZ shows enhanced antifungal activity (14)(15)(16) and was reported to inhibit the malignant phenotype of breast cancer cells (13).…”

“…Of these, SCZ is an antifungal agent with a broad spectrum of activity and is proposed for the treatment of skin infections such as dermatophyte infections (14)(15)(16). Compared to several imidazoles, SCZ shows enhanced antifungal activity (14)(15)(16) and was reported to inhibit the malignant phenotype of breast cancer cells (13). In this study we demonstrate the ability of SCZ to inhibit the expression of PD-1 on activated T cells and PBMCs through NF-kB activity and calcium mobilization repression.…”

<p>Development of sulconazole-loaded nanoemulsions for enhancement of transdermal permeation and antifungal activity</p>

“…Sulconazole (SCZ) is a broad-spectrum anti-fungicidal transdermally administered agent for treating skin infections, including dermatophyte infections, pityriasis versicolor and candidiasis with rare clinical use 1. In some trials, SCZ produced better antifungal activity than other drugs (Miconazole and Clotrimazole) for the treatment of candidiasis and tinea pedis 2. SCZ has shown promising prospects in preliminary clinical practice and might be a succedaneum or used in combination with other drugs, especially in cases where existing antifungal drugs have not been effective 3.…”

Analysis of Skin Disposition of Flurbiprofen after Topical Application Using Dual Agar Gel Discs-Inserted Rats

“…Such skin disposition of drugs (i.e., dermato-pharmacokinetics: DPK) is more important to evaluate topical formulations having local than systemic effects. 1,2) In addition, various physical means using a non-needle injection 3,4) and microneedle system 5,6) were developed to directly load drugs into the skin. These developments of technological advantages for direct delivery of drugs into the skin are increasing the importance of DPK.…”