RESUMEN
Calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories) is a new treatment for psoriasis. Calcitriol is the biologically active metabolite of vitamin D3. It induces keratinocyte differentiation, inhibits keratinocyte, T-cell and fibroblast proliferation, and inhibits the production of some inflammatory mediators, all contributors to the pathogenesis of psoriasis. Preclinical studies have shown an effect of topical calcitriol on calcium homeostasis at doses higher than those in clinical use. No adverse local events were observed when calcitriol was applied to animal skin. Phase I clinical studies confirmed that calcitriol 3 microg g(-1) ointment is well tolerated in humans. These studies have demonstrated that at the minimal effective concentration of 3 microg g(-1), calcitriol ointment has no discernible photosensitizing or phototoxic potential and no skin irritant or allergic potential in healthy volunteers. Its low systemic absorption through human skin is unlikely to significantly affect calcium homeostasis. This paper summarizes the findings of the preclinical and early clinical studies that provided the foundation of the later Phase II and III clinical trials on efficacy and safety with topical calcitriol 3 microg g(-1) ointment for the treatment of plaque psoriasis.
Asunto(s)
Calcitriol/uso terapéutico , Agonistas de los Canales de Calcio/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Cutánea , Animales , Calcitriol/efectos adversos , Calcitriol/farmacocinética , Agonistas de los Canales de Calcio/efectos adversos , Agonistas de los Canales de Calcio/farmacocinética , Relación Dosis-Respuesta a Droga , HumanosRESUMEN
Synopsis The distribution and dissociation of 14C-benzoyl-peroxide were studied in the skin of hairless rats after the application of a 10% gel during 3, 8 and 24 h. The distribution was appraised in the stripped horny layer and in the epidermis, and the dermis cut in slices parallel to the cutaneous surface. The conversion of benzoyl peroxide (b.p.) to benzoic acid (b.a.) was investigated from extracts of these different cutaneous layers by thin layer chromatography (TLC). The greatest amount of penetrating b.p. (9 to 14% of the applied dose) was found in the horny layer, which forms a reservoir and where biotransformations were reduced. Small quantities of b.p. diffused toward the epidermis down to the deeper dermis, where b.a. represented 74% of the radioactivity. Distribution gradients of the radioactivity and conversion rates to b.a. were stable between 3 and 24 h of application in all parts of the skin. This result showed that diffusion of b.p. from the vehicle was in balance with the dissociation processes and the blood resorption as b.a., throughout the experiment.