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.