Pharmacokinetics: the Key to the Problem

Hydroxychloroquine is the active ingredient in Plaquenil (Sanofi-Synthelabo Inc.) an anti-malarial drug that is also indicated for the treatment of  lupus erythematosus and rheumatoid arthritis. It is well recognized that response of these autoimmune diseases is very slow and researchers discovered the reason for this in a study that sheds considerable light on why the drug may not be living up to its promise in the current pandemic. The secret lies in the pharmacokinetics, which is a description of how easily a drug gets absorbed, the blood levels and tissues it reaches (and in what time period) as well as how long it lasts in the body before it gets changed or excreted. Here are some facts from a study of how the drug performs in healthy adults. [3]

• The drug is absorbed extremely well from an oral dose and peaks in the blood at about 3 hours.
• The drug is rapidly taken up by red blood cells (within seconds) and released into the plasma VERY slowly. In other words, the drug is sequestered in the blood cell compartment (which is why it works so well for malaria - a parasite infection within the red blood cells). This results in a 5 -fold lower concentration in the plasma, which in turn, is why it takes much longer for the drug to penetrate the tissues, like lung.
• It took 6 months to achieve 96% steady-state levels between blood and tissue when taking 155mg tablet daily, which explains why the symptom relief in rheumatoid arthritis and lupus may not be expected sooner.
• In treating CoVID-19 pneumonia, and particularly when hydroxychoroquine is started when the patient has advanced pneumonia, or has taken a turn for the worse and is heading for the ICU, giving the drug orally or even intravenously will result in the drug being trapped in the red blood cells and not be able to get
  into the lung tissues quickly enough to provide any benefit. It is often too late, sadly.

the Xeragenx Solution - Nebulized Chloroquine Inhalation

By delivering chloroquine to the lungs directly, via inhalation will circumvent the problem of oral or intravenous hydroxychloroquine from being trapped in the the blood cell compartment and not reaching the lungs in time. We are not just talking about blowing chloroquine into the lungs, but will be loading it onto a drug delivery system that may be successful at directing the drug to the cells that are in the front line of the battle with CoVID-19 - the M2 macrophages. These are the 'sentry cells protecting the pulmonary alveoli (air sacs) that express a specialized protein on their cell membrane, called the multi-ligand mannose receptor (or CD206) that is intimately involved in the complex inflammatory process . [4] CD206 is responsible for pathogen recognition, antigen presentation and clearance of foreign material (phagocytosis) in the alveoli. In other words, these ‘sentry cells’ are at the center of  this ‘cytokine storm’ and Xeragenx's drug delivery platform may facilitate docking of chloroquine to the M2 macrophage surface receptor to fight the virus. How do we do this? In collaboration with Prof. Robert Doyle at Syracuse University...

• Chloroquine is  conjugated (bound) to vitamin B12
• Chloroquine-B12  is bound to Xeragenx's recombinant human Intrinsic Factor (rh-IF) which binds to the M2 macrophage CD206 receptor [5] See Here
• Chloroquine-B12-rh-IF complex is put into an aerosolized 1-2ml solution and administered by nebulized mist directly into the lungs by inhalation
• A powerful anti-viral, anti-inflammatory administered directly, early on and at a fraction of the dose, avoiding the blood cell 'trap' as well as the higher systemic doses that are associated with cardiac and other serious side effects.