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.