Tretinoin: A Review of Its Anti-inflammatory Properties in the Treatment of Acne.

Tretinoin has been primarily used for the early stages of acne because of its proven comedolytic end benefits. This article reviews and updates the collective body of evidence of tretinoin in the treatment of acne, which suggests that this drug also possesses a broad range of acne-related immunomodulating properties that are capable of disrupting and hindering the various stages of the inflammatory cascade and the production of proinflammatory factors associated with it.

Clindamycin 1.2% Tretinoin 0.025% Gel versus Clindamycin Gel Treatment in Acne Patients: A Focus on Fitzpatrick Skin Types.

BACKGROUND: Acne vulgaris affects individuals of all races and ethnicities. Understanding the safety and efficacy of topical agents benefits the practicing clinician when treating patients with skin of color. PURPOSE: To report observations in acne patients representing all six Fitzpatrick skin types based on a Phase 3 study that evaluated the efficacy and safety of a clindamycin phosphate 1.2% tretinoin 0.025% gel versus a clindamycin phosphate 1.2% gel alone. METHODS: The two treatments were compared in a randomized, double-blind, multicenter, parallel, 12-week study employing a total of 2,010 patients with moderate-to-severe acne. Primary efficacy endpoints were 1) treatment success defined as percentage of patients who were clear or almost clear or achieved at least a 2-grade improvement in Evaluators Global Severity Scores at Week 12 and 2) percent change from baseline versus 12-week scores for noninflamed, inflamed, and total lesions. RESULTS: The 12-week, 37.8-percent Evaluators Global Severity Scores treatment success for clindamycin phosphate 1.2% tretinoin 0.025% gel was greater than the 31.7 percent observed for clindamycin phosphate 1.2% gel alone (P = 0.002). Percent changes from baseline versus 12-week scores for noninflamed, inflamed, and total lesions obtained with clindamycin phosphate 1.2% tretinoin 0.025% gel (49.8, 60.9, and 54.5%, respectively) were significantly greater than those observed for clindamycin phosphate 1.2% gel alone (41.3, 54.8, and 46.9%, respectively); all comparisons P<0.001. CONCLUSION: Use of clindamycin phosphate 1.2% tretinoin 0.025% gel resulted in greater percent reductions of Evaluators Global Severity Scores treatment success scores and acne lesions in patients with all six Fitzpatrick skin types combined than clindamycin phosphate 1.2% gel alone. Both products were well tolerated, with no hypo- or hyperpigmentation noted. Side effects observed were similar to those previously reported for the individual ingredients.

In vivo determination of the skin atrophy potential of the super-high-potency topical corticosteroid fluocinonide 0.1% cream compared with clobetasol propionate 0.05% cream and foam, and a vehicle.

PURPOSE: Prolonged topical corticosteroid use is often associated with atrophic skin changes. This trial compared signs of skin atrophy related to 3 super-high-potency corticosteroids: fluocinonide 0.1% cream, clobetasol propionate 0.05% cream, and 0.05% foam. PATIENTS AND METHODS: The test treatments were applied to the forearms 10 females twice daily for 21 days. Skin characteristics were assessed pretreatment and posttreatment for atrophic changes. Further punch biopsies obtained from 5 subjects were assessed histologically. RESULTS: Clobetasol foam produced mild changes in noninvasive tests, but stained skin biopsies revealed structural changes nearly comparable to clobetasol cream, which showed substantial atrophic changes. Fluocinonide cream was the least atrophogenic, producing no or only mild effects that were slightly greater than vehicle. CONCLUSIONS: Fluocinonide cream has a lower potential to produce atrophic changes of the skin than either clobetasol cream or clobetasol propionate foam.

Topical corticosteroids, structure-activity and the glucocorticoid receptor: discovery and development--a process of "planned serendipity".

This is a personal recounting of the way in which the original steroid chemists and biologists worked closely together, often by trial and error, to use cortisol as the template to develop increasingly improved systemic glucocorticoids. In doing this, they learned how certain chemical functional groups affected efficacy and safety negatively and positively. When the more promising systemic glucocorticoids were subsequently applied topically, the skin barrier impaired their activity. This led to new research, this time employing in vitro percutaneous absorption evaluations coupled with in vivo vasoconstrictor studies, to screen and develop effective new topical delivery systems. A subsequent stage of this glucocorticoid research revealed that these molecules had to "fit" into receptor sites and the approximate spatial structure of such receptor sites. It also disclosed the way that the various chemical functional groups affected that "fit" and the resulting effect upon safety and efficacy.

Ciclopirox delivery into the human nail plate.

The human nail penetration of the antifungal ciclopirox was determined for marketed gel containing 0.77% of ciclopirox, an experimental gel containing 2% of ciclopirox, and a marketed lacquer containing 8% of ciclopirox. After 14 days dosing, unabsorbed drug remaining on the surface, drug within the infection-prone area, and the amount that had penetrated through the nail were determined. Ciclopirox delivery into and through the nail was significantly greater from the marketed gel, than from either the experimental gel or the nail lacquer (p < 0.05). In addition, the surface nail contained more unabsorbed drug from the lacquer. Further, the drug penetrating into and through the nail was also greater from the marketed gel, leading to a higher Calculated Efficacy Coefficient for the marketed gel, than from the marketed lacquer or the experimental gel. The formulation plays an important role in the enhancement of ciclopirox permeation into and through the human nail plate, and the concentration of ciclopirox in the formulation was not a factor in determining penetration.