Phase 1 Randomized Placebo-Controlled Study in Healthy Adult Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate – A Potential Treatment for COVID-19

Source: The Journal of Allergy and Clinical Immunology


The airways and lungs are the primary sites of SARS-CoV-2 entry, replication, and damage, so there is reason to administer drugs to these regions.

Oral hydroxychloroquine (oHCQ) has produced mixed results in COVID-19, despite reported antiviral activity in vitro (EC50=0.72-119 μM).

We tested the hypothesis that aerosolized HCQ sulfate (aHCQ) tolerably, safely, and rapidly achieves high respiratory tissue concentrations, while minimizing systemic toxicity.


aHCQ was administered via Aerogen nebulizer (oral inhalation, nasal exhalation) to healthy volunteers in a Phase 1 study to assess tolerability, safety, and pharmacokinetics.


10 volunteers (age 55±13 years, 60% female) were randomized to Placebo (n=2), or aHCQ (20 mg, n=2; 50 mg, n=6); all completed the inhalation. 6/8 receiving aHCQ had adverse events (all mild; 75% transient dysgeusia, 25% dizziness). FEV1 and FVC were essentially unchanged from baseline after 15-360 minutes and 1 and 7 days. QT segments were minimally changed from baseline (maximum change 34 msec) after 1-6 hours, and 1 and 7 days; all were ≤455 msec. 

Pharmacokinetics of 50 mg: Area Under the Blood Curve 0-24 hours post-inhalation was 377±127 ng*hr/mL, <15% of that reported for oHCQ 200 mg; Pharmacokinetic modelling predicts initial epithelial lining fluid concentrations in excess of reported EC50s, and peak respiratory tissue concentrations of 0.5 mM, decreasing to 0.01 mM at 24 hours as HCQ slowly releases into blood.


aHCQ was safe, well-tolerated, and appears to be sequestered in respiratory tissues. Administering aHCQ at a fraction of oral dosing may rapidly achieve respiratory tract concentrations sufficient to inhibit SARS-CoV-2.

Related: Journal of Medicine Says HCQ + Zinc Reduces COVID Deaths

Yale doctor slams Fauci for his dismissal of hydroxychloroquine in COVID treatment

HCQ Peer-reviewed: Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

Hydroxychloroquine and Ivermectin: The medical establishment’s war on COVID therapeutics

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk COVID-19 infection includes HCQ & Ivermectin

Share on facebook
Share on twitter
Share on whatsapp
On Trend

Latest Stories

A Conversation With Dr. Brian Tyson – The Chloroquine Wars Part XLI

The data from the vaccine trials must be recalculated under the lens that some of the serious adverse events (SAEs) should be treated as COVID-19 cases.
There may not be any vaccine efficacy in the data at all if some of the post-vaccination deaths are due to vaccine-induced COVID-19. It could even be the case that the mortality efficacy goes negative. My implied lives saved calculations put this easily in the realm of possibility. The only way to know is for authorities to organize and compile the data. And while a risk analysis is certainly due after more than six months of hundreds of millions of doses delivered, there is little indication authorities have bothered with the process. That’s more than a bit unsettling.

Read More »

Dr. Brian Tyson, USA: Hydroxychloroquine – Data, Strategies and Success Treating over 6000 Covid Patients

We continue to delve extensively into the COVID-19 data with esteemed statistician, Mathew Crawford. In this episode, we take a closer look at the use of early treatment and its success. Mathew has been researching the data from Dr. Brian Tyson, who has successfully treated over 6000 patients who contracted COVID throughout the pandemic. It is my great honor to have Dr. Tyson here on this episode to not only discuss the data, but also the strategies that he has been using throughout the pandemic.

Read More »