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 D3 (tacalcitol) and 1 alpha,25-dihydroxy-vitamin D3 (calcitriol) was compared in a hairless guinea pig model, Randomized, occlusive patch testing for 2 days was used. Each group of 8 animals was tested simultaneously with the 3 substances and a placebo vehicle. 3 dose levels i.e. 500 micrograms/ml, 50 micrograms/ml and 5 micrograms/ml were used. Test sites were evaluated at day 2 (2 h after removal of the patches) and again at day 3. Evaluation 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 ChromaMeter) and skin thickening (20 MHz ultrasound) indicating oedema. Skin biopsies were taken for histological preparation and assessment of epidermal hyperplasia. No difference was observed between the irritant potential for calcipotriol, tacalcitol and calcitriol based on clinical scoring as well as objective non-invasive measuring techniques. All 3 substances showed a dose-dependent and equal increase in clinical irritation score, cutaneous blood flow, skin colour and epidermal hyperplasia. The cutaneous inflammatory reaction was dominated by vasodilation and increased cutaneous perfusion. Oedema formation was only seen at the highest dosages tested. Skin barrier damage was not induced as TEWL remained unaffected. The hairless guinea pig appears a valid model to test irritancy of topical D-vitamins since the same profile of irritancy was previously established in humans for 2 of the compounds tested, calcitriol and calcipotriol.
Fullerton
A
A
Department of Dermatological Research, Leo Pharmaceutical Products, Ltd., Ballerup, Denmark.
Serup
J
J
D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D017453:Dermatitis, Irritant / Q000209:etiology*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000633:toxicity*; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D017078:Laser-Doppler Flowmetry; D010328:Patch Tests; D011897:Random Allocation; D012016:Reference Values; D012867:Skin / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
D003879:Dermatologic Agents; D004100:Dihydroxycholecalciferols; C055085:calcipotriene; C023850:1 alpha,24-dihydroxyvitamin D3; D002117:Calcitriol