Its administration by different route is well described in rodents and humans. In particular:(a) Chronic administration (about 4 weeks) of C-16/DLM-4760 in combination with ACE2 activating treatments was performed by daily intraperitoneal injection at a dose of 25mg/kg in distilled water (as a solution of 42 mg/mL) or 0.9% sterile saline (as a solution of 84 mg/mL using a 0.5-mL insulin syringe) freshly prepared [52,183,184].
(b) Alternatively, chronic administration (about 8 days) of GL1001/DLM-4760 disodium salt in combination with an ACE2 activating treatment was performed by subcutaneous injection (5mL/kg) containing up to a dose of 300 mg/kg, twice a day, formulated in a vehicle solution [15% 2-hydroxypropyl-β-cyclodextrin (HPBDC)/85% H2O] [122]. Subchronic doses of GL1001 indicate no adverse effects up to 1,000 mg/kg (see [122]).
(c) In humans ORE1001/GL1001/MLN-4760 was already proposed and tested in clinical trials. Its pharmaceutical indication was for digestive tract inflammations (Inflammatory bowel disease, gastritis and colitis) that are correlated with overexpression of ACE2. In a Phase I clinical testing up 14 days dosing, ORE1001 was well tolerated. Subjects received drug (dosing up to 2100 mg) with no side adverse effects reported. In particular, 47 subjects received single-dose from 2.1 to 2100 mg and 24 subjects received 14 day multiple doses from 50 mg to 1800 mg. All doses were well tolerated, with no significant side effects including blood pressure. Pharmacokinetics of orally administered capsules was consistent with once-daily dosing. (http://oreholdings.com/wp-content/uploads/2013/06/09.10.09-425.pdf). 300 mg (active drug) oral capsules were used in a Phase Ib/IIa clinical trial that was, however, abandoned. (https://clinicaltrials.gov/ct2/show/NCT01039597).
(d) Finally, MLN-4760 was also administered (2.5 mg/kg per day) by nasal inhalation for 2–3 days in lung-infected mice by Pseudomonas bacteria [185]. Interestingly, the report underscores the role played by local concentration of molecules (ACE2) in modulating lung inflammation and disease. For these reasons, in diseases involving respiratory tract, like SARS, inhalation treatment is preferable, even for the lower concentration (and hopefully lower toxicity) of MLN-4760 needed for this route of treatment administration.