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/m2 per application for ointment base and 40 g/m2 per application for cream. At this dosage, an average individual would use approximately 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)/m2 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.
Osborne
J E
JE
The Department of Dermatology, Leicester Royal Infirmary, UK. joyos@doctors.org.uk
Hutchinson
P E
PE
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000886:Anthropometry; D015992:Body Mass Index; D002117:Calcitriol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy*; D012494:Sampling Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D017211:Treatment Failure; D016896:Treatment Outcome; D006113:United Kingdom
D003879:Dermatologic Agents; C055085:calcipotriene; D002117:Calcitriol