Lung pharmacokinetics of inhaled and systemic drugs: A clinical evaluation

Abstract

United Kingdom) for scientific exchange and technical advice. We thank the clinical study volunteers for their participation and the site staff for their diligent study conduct. We also thank Richard Claes, PhD, of PharmaGenesis London (London, United Kingdom) for providing medical writing support, which was funded by AstraZeneca (Gothenburg, Sweden) in accordance with Good Publication Practice 3 (GPP3) guidelines (http://www.ismpp.org/gpp3).

Oral inhalation of cannabidiol delivered from a metered dose inhaler to alleviate cytokine production induced by SARS-CoV-2 and pollutants

“…Thus, it was quite difficult to justify a suitable daily dose [ 24 , [27] , [28] , [29] ]. In a recent phase 1 clinical study of CBD dry powder inhaler, the authors reported a C max of 18.78 ng/mL of CBD [ 30 ], and in general the lung drug concentration should be about 100-fold higher than the concentration in the plasma [ 31 ]. Also, it is worth noting that the extravascular lung fluid according to various reports is about 2–10 mL [ 32 , 33 ].…”

Discovery of peptides for targeted delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia

“…For diseases affecting the lungs, such as cystic fibrosis (CF), local delivery of therapeutics is promising since it results in fewer systemic side effects, requires a lower dose compared to systemic delivery, and therapeutics can be administered in multiple ways that are amenable to outpatient use (e.g., nebulizer, dry powder, metered-dose inhaler). (3, 20–23) For example, when comparing inhalation versus oral delivery of the same drug substance, lung: plasma drug concentration ratios can reach over 100 (compared to 1.6 for oral administration), making local delivery advantageous for targeting the lung tissues. (23) For CF, this pharmacokinetic profile is attractive for the delivery of gene therapies like CFTR gene replacement or correcting specific CFTR mutations.…”

“…(3, 20–23) For example, when comparing inhalation versus oral delivery of the same drug substance, lung: plasma drug concentration ratios can reach over 100 (compared to 1.6 for oral administration), making local delivery advantageous for targeting the lung tissues. (23) For CF, this pharmacokinetic profile is attractive for the delivery of gene therapies like CFTR gene replacement or correcting specific CFTR mutations. However, both mucus and cell barriers hinder transport and delivery of therapeutics into the cell.…”

A new method for investigating bioequivalence of inhaled formulations: A pilot study on salbutamol

“…Although the results of this small-size pilot study were promising, we had two main limitations; i.e., only one tobramycin inhaled formulation was available, and we used an analytical method with low sensitivity and selectivity, which resulted in wide variations of EBC concentration profiles of six healthy volunteers ( 12 ). In another interesting work, Sadiq et al ( 13 ) investigated the lung pharmacokinetics of several inhaled and orally administered drugs including salbutamol. They measured the levels of salbutamol in plasma, epithelial lung lining fluid (ELLF), bronchoalveolar lavage (BAL) and in some cases in the filters adsorbing the exhaled particles.…”