To determine a schedule for continuous suppression of epidermal cell DNA synthesis, 0.05% fluocinonide ointment was applied either twice daily or once on alternate days to hairless mouse skin for 174 hours. Suppression occurred similarly for both regimens for 78 hours followed by an increase in DNA synthesis despite continued application of fluocinonide. The systemic effect was less marked with the alternate-day schedule. The effect of a single application of the fluocinonide ointment was also studied over 174 hours. Substantial inhibition of DNA synthesis occurred but for a shorter period followed by an increase and then return to normal values. Experiments were performed where second applications were made at various time intervals after the first. These did not appear to affect events until 192 hours had elapsed, when a second application caused profound inhibition of DNA synthesis once more.

Summary DNA synthesis in hairless mouse epidermis was studied during twice daily and 72‐hourly application regimes of Metosyn, Betnovate and Dermovate ointments, and of 0.05% fluocinonide solution, in order to determine a treatment schedule for continuous suppression of epidermal cell DNA synthesis. Tachyphylaxis occurred with all the twice daily regimes but not with the 72 hourly application regimes of Dermovate and Betnovate ointments during the time of study. The onset of tachyphylaxis was delayed when fiuocinonide was applied in solution as opposed to ointment (Metosyn) form. Varying the steroid preparation within a 72 hourly application regime did not prevent the development of tachyphylaxis by 150 h.

The hairless mouse was used to investigate the effects of a combination of glucocorticosteroid with either dithranol or tar on epidermal DNA synthesis, in order to determine whether such combinations reduce epidermal DNA synthesis more effectively than the single agents. Dithranol alone produced a significant local inhibition of DNA synthesis at concentrations of 0.1% and 0.05% but not at lower concentrations. Dose-response data for dilutions of clobetasol propionate and betamethasone 17-valerate showed progressive diminution of both local and systemic effects with decreasing concentrations. An additive effect was found from combining clobetasol propionate with dithranol and from combining betamethasone 17-valerate with liquor picis carbonis. These combined preparations were tested again after storage for 6 months and 2 months respectively and showed no loss of efficacy. These results lend justification to the use of these combined preparations in the treatment of psoriasis.

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