S. Hill

The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin

Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol® fine and Brasivol® medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride‐induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment.

Relief of experimentally induced pruritus with a novel eutectic mixture of local anaesthetic agents

The effectiveness of a eutectic mixture of the local anaesthetics lignocaine and prilocaine (EMLA® cream) in relieving artificially induced pruritus was examined in 20 volunteers. The study was conducted in two parts. In part one, the effect of EMLA on the threshold concentration of histamine necessary to induce pruritus was assessed by a double‐blind placebo controlled method. In part two, the effect of EMLA on the perception of pruritus induced by the artificial pruritogens cowhage and papain was assessed by a single blind method.

An investigation of the pharmacokinetics of topical terbinafine (Lamisil®) 1% cream

Summary Twenty human volunteers were entered into a study to investigate the pharmacokinetics of terbinafine 1% cream. Subjects were randomized to receive terbinafine 1% cream applied to the back on 1 day, or on 3, 5 or 7 consecutive days. Up to five sequential skin surface biopsies were taken at a site on the upper back at various time‐points both during treatment, and following cessation of treatment. Terbinafine levels in these biopsies were analysed using HPLC. The study showed that increasing the number of applications from one to seven did not significantly increase the peak concentration (Cmax) in the stratum corneum. It did, however, increase the total amount of terbinafine found in the stratum corneum, resulting in terbinafine being detected for longer periods after cessation of therapy. Treatment for 7 days resulted in terbinafine still being detectable 7 days after cessation of therapy, when the terbinafine concentration was significantly higher than the known cidal concentrations for the common causative organisms of superficial dermatomycoses. This study indicates a significant potential for short‐duration treatment with terbinafine (Lamisil®) 1% cream in superficial dermatomycoses.

Investigations on the Percutaneous Absorption of the Antidepressant Rolipram in Vitro and in Vivo

In vitro experiments using full-thickness human skin showed that it was feasible to deliver therapeutic amounts of the new antidepressant drug rolipram. Simple transdermal devices were constructed, and the presence of isopropyl myristate (IPM) in a silicone adhesive (Dow Corning X7-2920) enhanced the flux across excised human skin. The steady-state fluxes from adhesive mixtures containing 0, 5, and 10% IPM were 3, 5.2, and 6 µg/cm2/hr, respectively. The in vitro experiments were confirmed in a clinical study involving six healthy male volunteers. The formulations tested were an alcoholic solution and adhesive patches containing 5 and 10% IPM. The dose of drug administered was 0.5 mg/cm2 and the device size 25 cm2. Blood samples were withdrawn over a 24-hr period and analyzed using radioimmunoassay. The topical applications were well tolerated, with only mild or no side effects. A lag time of approximately 2 hr was found for the detection of rolipram in the plasma (detection limit, 50 pg/ml). Interindividual variations both for the peak drug levels and throughout the delivery were quite high but this magnitude of variation has been observed in many other transdermal studies. Plasma levels between 1 and 2 ng/ml were found for all formulations and the AUC0–30hr was significantly higher for the patch containing 5% IPM.

Portable erythema meter and its application to use in human skin.

In this study a compact, hand‐held, solid state erythema meter using light emitting diodes is described. This device has been constructed and used to compare with visual assessments of ultraviolet radiation in human subjects. A statistically significant correlation was obtained between erythema index and visual assessment in 24 ultraviolet irradiated subjects. Furthermore, the effects of three aftersun treatments have also been assessed objectively using the meter and subjectively using visual assessments. The ultraviolet‐irradiated areas were less red following treatment than the irradiated and untreated areas. The results obtained by the meter were similar to and statistically significant with those obtained by visual assessment.

The effect of area of application on the intensity of response to a cutaneous irritant

Summary The intensity of the cutaneous response was assessed after application of a standard irritant to increasing areas of normal forearn skin. Twenty subjects were tested to determine the minimal irritant does (MID) to dilutions of aqueous sodium dodecyl sulphate. Each subject was then treated under occlusion for a period of 24 hours with different areas of filter paper (9.25,100, 225 and 400 mm2) soaked with the concentration required to give the individuals MID. At 25 and 48 hours the degree of erythema was assessed using a 0–4 arbitrary scale, a 10‐cm visual analogue scale (VAS) and an erythema meter. Cutaneous blood flow was measured with a laser‐Doppler device and cutaneous oedema measured by pulsed A‐scan ultrasound. The results at 25and 48hours were almost identical. Both forms of visual assessment (arbitrary scale and VAS) showed an increase in perceived erythema with increasing area and this was confirmed by the erythema meter. Further area‐related changes were noted with both cutaneous blood flow and ultrasound measurements.

Effects of Cetirizine, Loratadine and Terfenadine on Histamine Weal and Flare Reactions

This randomised double-blind, placebo-controlled, cross-over study compared the effects of single oral doses of terfenadine 120 mg, cetirizine 10 mg, and loratadine 10 mg on experimentally induced weal and flare reactions. The areas of weal and flare induced by intracutaneous injections of histamine were measured using planimetry, weal thickness by A-scan pulsed ultrasound and erythema index by a device which measures the relative reflectance of red and green light. All three antihistamines suppressed the weal and flare area and weal thickness 3, 6, 12 and 24 h after dosing. At the usual currently recommended doses terfenadine and cetririzine were most effective after 6 h and were more potent than loratadine for the first 6 h of the study.

Pharmacokinetics of Topically Applied Metronidazole in Two Different Formulations

Topical metronidazole is effective in the treatment of papulo-pustular rosacea, a common inflammatory disease of the face. In this study, a comparison of the bio-availability of two topical formulatio

Efficacy of topical dimetindene in experimentally induced pruritus and weal and flare reactions

Double-blind, placebo-controlled studies were performed to assess the effect of 0.1% dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release.