Novel crystalline tretinoin and clindamycin formulation delivers active ingredients with less irritation Abstract P133. American Academy of Dermatology 65th Annual Meeting February 2-6, 2007

Abstract

Background: A novel formulation of solubilized 1.2% clindamycin phosphate and crystalline 0.025% tretinoin aqueous gel was developed to provide a low level of retinoid-related irritation. Objectives: To determine the systemic penetration of crystalline tretinoin and clindamycin and to evaluate the potential for retinoid-related skin irritation compared with another retinoid gel. Methods: Two studies were conducted. In the first study, a single-center, open-label, multiple dose pharmacokinetic trial, 12 patients with acne vulgaris on the face, chest, and back applied 4 g of the combination product on all affected areas for 14 days. Predose blood samples were drawn. On day 14, blood was drawn at 2, 4, 6, 8, 10, 12, and 24 hours postdose. In a second study, the irritation potential of the novel combination was compared with a tretinoin 0.025% gel in a single center, evaluatorblind trial of repeated topical applications to healthy subjects. Test materials were applied under occlusive patches 3 times per week for 3 weeks. Evaluations were made at 48 or 72 hours for signs of irritation. A total irritation score based on a 0 to 4 scale for each product was calculated by totaling subjects� scores from all evaluation days. Results: In the pharmacokinetic study, very low levels of the drug were systemically available. If detectable at all, clindamycin concentrations ranged from 0.5 (LOQ) to 13.1 ng/mL over the course of the study. Tretinoin and 13-cis-retinoic acid levels ranged from 1.0 (LOQ) to 1.6 ng/mL over the course of the study. There was no statistically significant increase in plasma levels of clindamycin, tretinoin, or 13-cisretinoic acid on days 1 through 14. In the irritation study, the combination product was highly statistically significantly less irritating than the standard tretinoin formulation (P\.001). Conclusions: The novel formulation of crystalline tretinoin delivers tretinoin through the skin with very low levels of systemic exposure to each drug in the combination product. The crystalline formulation appears to significantly limit retinoid-related irritation compared with a solubilized retinoid formulation. Thus, use of the crystalline formulation may provide a tretinoin delivery method that has