The importance of accurate dosage of topical agents: a method of estimating involved area and application to calcipotriol treatment failures

Little attention is given to accurate dosage of topical medication which is a potential source of side-effects and treatment failure. There are studies on the dosage for 'sparing' application. relevant to topical steroids but not for 'liberal' application. Though calcipotriol is a first line topical treatment for psoriasis, approximately one-third of patients do not respond adequately. The aims of the present study were to define liberal dosage, to develop a method of calculation of area of involved skin and to evaluate the efficacy of calcipotriol in optimized liberal dosages, based on preliminary studies, in calcipotriol treatment failures. Weight/unit area of ointment and cream base, constituting liberal application, was determined in six normal volunteers. The area of psoriatic involvement in 24 calcipotriol non-responders was estimated by a 'fill-up' method and a modified 'hand' method. The results of the two methods were similar (Pearson correlation coefficient 0.68, P < 0.0001) but the 'hand' method proved easier in use and was the preferred method for the rest of the study. The patients applied calcipotriol at their accustomed rates for at least 2 weeks and then at the calculated liberal rates, using cream in the morning and ointment at night, for 4 weeks. The efficacy measures were Psoriasis Area and Severity Index (PASI) (primary measure), a four-point efficacy score and a visual analogue scale. As a result of the preliminary study and the actual amounts used by the patients in,the psoriasis treatment study reported below, liberal application has been defined as 50 g/m(2) per application for ointment base and 40 g/m2 per application for cream. At this dosage, an average individual would use approximate to 100 g of medication/week to treat 10% of the body surface. During the 4-week treatment study, the psoriasis patients used an average of 39 g (SD 17 g)/m(2) per application of cream and 52 g (SD 13 g)/m2 per application of ointment. All efficacy measures showed marked improvement (P < 0.0001). The frequency distribution of the PASI reduction defined responsive (70% of patients) and poorly responsive groups. (30%), with mean PASI reduction of 60% and 17%, respectively.