Effects of Calcipotriol (MC 903) and Calcitriol after Topical Application on the Skin of Hairless Rats

Abstract

Topical application of calcitriol or its analogs is a new approach for treating psoriasis, but may be limited by systemic calcitropic effects. Calcipotriol (MC 903) is a novel calcitriol analog with low calcitropic potency after systemic application. To compare the topical potency of calcitriol and calcipotriol we applied the two drugs on the right flanks of hairless rats for 10 days. In concentrations of 0.001-0.01 g/100 ml (ethanol) the two drugs are equally effective in inducing changes in the horny layer of the skin (increase in the amount of horny material that is able to be desquamated). This can be interpreted as a stimulation of terminal keratinocyte differentiation. However, only calcitriol caused a significant rise in the serum calcium concentration. In conclusion, calcitriol and calcipotriol seem to be equally effective after topical application on the skin of hairless rats, but calcipotriol has a much lower systemic calcium liability.

Comparison of Calcipotriol with Selected Metabolites and Analogues of Vitamin D3: Effects on Cell Growth Regulation in Vitro and Calcium Metabolism in Vivo

“…Similar results have been obtained after dermal administration of calcipotriol and 1a,25(OH),D3 to hairless rats (Brautigam et al 1992). In these experiments both compounds were equally effective in stimulating terminal differentiation of keratinocytes.…”

Enhancement of the Antiparakeratotic Potency of Calcitriol and Tacalcitol in Liposomal Preparations in the Mouse Tail Test

“…The reason for the lack of a more potent response with higher concentrations in petrolatum might be due to the formation of a steady drug depot in the horny layer during the 14 days of treatment, which is limited by the saturation level of the horny layer. Thus, 10 and 100 Ìg/ml calcitriol and calcipotriol solved in ethanol were equally effective on the terminal differentiation in hairless rats when applied for 10 days [18].…”

Calcipotriol ointment shows comparable efficacy to topical steroids in chronic hand eczema

“…The main mechanisms of the biological effects of vitamin D (i.e., suppression of keratinocyte proliferation, regulation of keratinocyte differentiation, and modulation of the release of inflammatory cytokines) may culminate in the inhibition of keratinization and inflammation in CHE. Scaling may be the result of the stimulation of terminal differentiation of keratinocytes (Brautigam, Hubner, Rach, & Thieroff‐Ekerdt, ). Due to their potent anti‐inflammatory, antiproliferative and immunosuppressive properties, corticosteroids boost clinical resolution from the initiation of treatment.…”