3. Drug exhalation by the lungs
In pharmacology, drug metabolism and elimination in the lungs are not
well studied. However, it is possible to consider the elimination
process from a “drug delivery” rather than a “drug elimination”
point of view.
The ability of a drug to cross cell membranes depends on its partition
coefficient. The partition coefficient of a substance depends on its
chemical-physical characteristics; hydrophilic groups refer to those
that are capable of forming hydrogen bonds with water, such as the
carboxylic, alcoholic, amino, aldehyde and ketone groups and
electrically charged groups. The partition coefficient of a drug (i.e.,
its ability to cross cell membranes) can vary due to metabolization
processes. Generally, the systemic metabolization processes lead to the
formation of more hydrophilic compounds with partition coefficients
lower than those of the original drugs. Furthermore, it is important to
remember that many drugs are organic molecules that contain acidic or
basic residues, that is groups which, depending on the pH of the
solution in which they are found, can be electrically neutral or
charged. For these drugs, the partition coefficient is also dependent on
the pH of the environment and the pKA of the reactive groups.
The diffusion of drugs follows Fick’s law, so a drug with an adequate
partition coefficient can diffuse through cell membranes. The laws
governing the diffusion between two compartments separated by a membrane
are described by Fick’s law: molar flow = (c1- c2) ⊇ D ⊇ A/d wherein by
molar flow is meant the speed (moles per second) of the passage of a
solute from compartment 1 to compartment 2; c1 and c2 are the
concentrations of the compound in the two compartments; D is the
diffusion coefficient, which depends on the chemical-physical
characteristics of solvent and solute (in the case of passage through
biological membranes, D is mainly determined by the partition
coefficient); A is the area of the membrane that separates the two
compartments, and d is its thickness. In the case of the plasma
membrane, d can be considered a constant; in the case of a tissue, d
depends on the number of cell layers to be overcome.
Knowledge of this physiological mechanism could be useful in the review
of possible molecules with low pharmacodynamic specificity towards the
virus but with a high tropism for pulmonary elimination. The site of
action in this case becomes the first element of pharmacological
advantage over the aetiopathological agent.