The challenge of repurposing niclosamide: Considering pharmacokinetic parameters, routes of administration, and drug metabolism

Niclosamide is an anthelmintic drug approved by the Food and Drug Administration (FDA). The molecule has brought attention as a potential antiviral, antibacterial, and chemotherapeutic agent, among other indications. This myriad of therapeutical options is mainly due to niclosamide's physicochemical properties (i.e., pKa, LogP, and LogD); the molecule targets and accumulates in acidic environments such as those found in tumors and intracellular vesicles which are used by some viruses during their replication process. To date, several research articles have presented pharmacokinetic parameters after intravascular and oral administration of niclosamide. Unfortunately, niclosamide has a very low oral bioavailability which has typically been attributed to its low water solubility. However, herein we discuss niclosamide's metabolization and rapid clearance, which mainly occurs in the liver and small intestines. In general, most research articles conclude that niclosamide is safe. However, there is a lack of research published on acute toxicity or necropsies related to the novel and highly bioavailable formulations of niclosamide. Currently, several niclosamide formulations for oral, nasal, and pulmonary administration are being studied in clinical trials to treat cancer and viral infection. These clinical trials have resulted in the publication of some interesting pharmacokinetic parameters discussed in this document. The purpose of this paper is to provide a comprehensive review of studies published on the topic of repurposing niclosamide which often involves innovative formulation strategies.