Losartan preclinical safety assessment

On March 19,2020 we conducted an urgent pre-clinical animal safety assessment  by administering to a swine Losartan-N aerosol, delivering approximately 270 micrograms of active ingredient over a period of 30 minutes.

A miniature pig weighing  approximately  45-50 kg was intubated after intravenous administration of zoletil 100 (33 mg/kg dosage).  The animal was put on a ventilator and an introducer was placed in the right external jugular vein. Anesthesia was maintained by a continuous infusion of propofol at a rate of 10 ml/h. A Swan-Ganz catheter was placed through the introducer in the right heart ventricle. Cardiac output and congestion pressure in the pulmonary artery were measured by thermodilution.

The following parameters were measured before, during and after the inhalation: blood gases, pH,  sodium, potassium, calcium,  and glucose concentrations. Upon the placement of the catheter, the animal was transferred to spontaneous breathing, but remained unconscious (administration of zoletil and propofol). The drug was delivered over a period of 30 minutes through spontaneous breathing by feeding aerosol directly, using a narrow tube inserted into the intubation tube.

All the measured parameters remained unchanged throughout the experiment.

Losartan preclinical safety assessment           

Finally, after the end of the aerosol inhalation, the anesthesia was stopped. Recovery from anesthesia was uneventful.  The animal appeared in good health for the entire period of observation after the experiment (7 days).