A Promising Approach to Treat Psoriasis: Inhibiting Cytochrome P450 3A4 Metabolism to Enhance Desoximetasone Therapy

(1) Background: Human keratinocytes and murine skin express various Cytochrome P450 enzymes. These include Cytochrome P450 3A4, which may participate in the metabolism of Cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and Cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting Cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01-0.05% desoximetasone loaded into a Cytochrome P450 3A4 Enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a Cytochrome P450 3A4 Enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg/gm clobetasol ointment. (4) Conclusions: The Cytochrome P450 3A4 Enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of Cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.

cytochrome P450 3A4; desoximetasone; microemulsion; psoriasis; skin barrier; topical.