Indications
Crisaborole is approved for the topical treatment of mild to moderate atopic dermatitis in patients aged two years and older. This non-steroidal ointment offers a therapeutic option for managing the symptoms and signs of atopic dermatitis, providing effective relief for affected individuals.
Pharmacodynamics
Crisaborole exerts its therapeutic effects through its broad-spectrum anti-inflammatory activity. The primary mechanism of action involves the inhibition of the enzyme phosphodiesterase 4 (PDE4), which plays a significant role in the regulation of inflammatory cytokine production. By targeting this enzyme, crisaborole mediates an anti-inflammatory effect across various inflammatory cells, including those found in keratinocytes and immune cells. Due to its topical application, the drug effectively localizes within the skin, exerting its anti-inflammatory effects at low micromolar concentrations.
Absorption
Upon twice-daily topical administration, systemic concentrations of crisaborole are achieved within eight days. The drug demonstrates low systemic absorption, which minimizes the potential for systemic side effects, allowing for safer use in the indicated patient population.
Metabolism
Crisaborole undergoes substantial metabolism, resulting in the formation of inactive metabolites. The primary metabolite, 5-(4-cyanophenoxy)-2-hydroxyl benzylalcohol (known as metabolite 1), is produced through hydrolysis. This metabolite is subsequently metabolized into further downstream products, including 5-(4-cyanophenoxy)-2-hydroxyl benzoic acid (metabolite 2), which is formed through oxidation and constitutes another major metabolite in crisaborole's metabolic pathway.
Mechanism of Action
Crisaborole functions as an inhibitor of phosphodiesterase 4 (PDE4), resulting in elevated concentrations of cyclic adenosine monophosphate (cAMP) within cells. This increase in cAMP levels leads to the inhibition of the NF-kB pathway, consequently suppressing the release of pro-inflammatory mediators such as TNF-alpha and various interleukins, which are implicated in the pathogenesis of psoriasis and atopic dermatitis. The therapeutic efficacy of crisaborole in treating immune-mediated skin conditions can be attributed to its ability to mitigate these downstream effects across different cell types.
