TOPICAL D-VITAMINS - MULTIPARAMETRIC COMPARISON OF THE IRRITANT POTENTIAL OF CALCIPOTRIOL, TACALCITOL AND CALCITRIOL IN A HAIRLESS GUINEA-PIG MODEL

The irritant potential of calcipotriol, 1 alpha,24-dihydroxyvitamin D- 3 (tacalcitol) and 1 alpha,25-dihydroxyvitamin D-3 (calcitriol) was co mpared in a hairless guinea gig model. Randomized, occlusive patch tes ting for 2 days was used. Each group of 8 animals was tested simultane ously with the 3 substances and a placebo vehicle. 3 dose levels i.e. 500 mu g/ml, 50 mu g/ml and 5 mu g/ml were used. Test sites were evalu ated at day 2 (2 h after removal of the patches) and again at day 3. E valuation was blinded and based on a multiple parameter assessment of skin irritancy, comparing clinical scoring, skin perfusion using high resolution laser Doppler image scanning, skin colour (a, Minolta Chro maMeter) and skin thickening (20 MHz ultrasound) indicating oedema. Sk in biopsies were taken for histological preparation and assessment of epidermal hyperplasia. No difference was observed between the irritant potential of calcipotriol, tacalcitol and calcitriol based on clinica l scoring as well as objective non-invasive measuring techniques. All 3 substances showed a dose-dependent and equal increase in clinical ir ritation score, cutaneous blood flow skin colour and epidermal hyperpl asia. The cutaneous inflammatory reaction was dominated by vasodilatio n and increased cutaneous perfusion. Oedema formation was only seen at the highest dosages tested. Skin barrier damage was not induced as TE WL remained unaffected. The hairless guinea pig appears a valid model to rest irritancy of topical D-vitamins since the same profile of irri tancy was previously established in humans for 2 of the compounds test ed, calcitriol and calcipotriol.