Intramuscular injections
To address concerns around poor oral bioavailability of niclosamide, a formulation administered via the intramuscular route was developed. It is currently being investigated in healthy volunteers to assess its safety, tolerability, and pharmacodynamics and pharmacokinetics (PK/PD) in 40 COVID-19 patients (Table 2). This trial is a multiple-dose ascending study injecting different volumes of a 24% suspension at four predefined injection sites. Incidence of treatment-emergent adverse events and time to- and rate of- eradication of SARS-CoV-2 are the primary and secondary endpoints, respectively. Notably, Choi et al., (2021) performed a PK study in rats comparing equal doses of niclosamide administered via the intramuscular, intravenous and oral routes. They found increased systemic exposure with the intramuscular injection with a 70-fold higher Cmax and 13-fold higher AUClast compared to the oral route. The intramuscular bioavailability was found to be 65% compared to 5.5% via the oral route, highlighting the substantial improvement via the intramuscular route.