A Novel Drug Delivery Method: Retrometabolic Drug Design

Soft drugs, a class of retrometabolic drug design, contain a metabolically sensitive moiety that promotes rapid metabolism to inactive metabolites after exerting activity at its target site. The goal of soft drugs is to reduce systemic toxicity while enhancing local efficacy. Soft drugs have been approved for use in multiple medical specialties, such as the soft corticosteroid loteprednol etabonate for treatment of inflammatory ophthalmic disorders and soft beta-blocker derivatives for treatment of hypertensive emergencies in cardiology. Soft drugs have also found widespread use in the field of dermatology. In the setting of topical drug administration, soft drugs minimize the risk of systemic drug absorption and unwanted side effects. Soft janus kinase caspase 1 (JAK) inhibitors, soft transient receptor potential vanilloid (TRPV1), and soft estrogens among others have been explored as therapeutic options for a variety of inflammatory and autoimmune dermatologic conditions. The soft anticholinergic sofpironium bromide represents the latest expansion of soft drug use in dermatology for the treatment of primary axillary hyperhidrosis (PAH). A derivative of glycopyrronium, sofpironium bromide consists of a chemically modified structure that allows the drug to undergo rapid hydrolytic deactivation, and thus minimize the significant side effects associated with traditional anticholinergic drugs. Sofpironium bromide has demonstrated efficacy and safety for treatment of PAH in Phase II and Phase III clinical trials in Japan and the United States. Given the promising results from these studies, sofpironium bromide, in addition to other soft drugs under investigation, highlights the growing utility of retrometabolic drug design in dermatology. J Drugs Dermatol. 2022;21:4(Suppl 2):s5-10.