Source: Annual Congress 2003 - Respiratory structure and mechanisms: current concepts

Abstract

Aim: To analyse the structure-absorption relationships for pulmonary delivered drugs. Methods: I) A profile of calculated physicochemical properties of inhaled drugs on the market during 2001 was made. II) An in vivo pharmacokinetic investigation was performed in anesthetized rats. Eight selected drugs were administered intravenously and by intratracheal nebulization and the plasma concentrations of the drugs were determined by LC-MS-MS. III) An evaluation of the relationships between the absorption/bioavailability data and the drugs’ physicochemical properties and the epithelial permeability in Caco-2 cells (P_app), respectively, was performed.
Results: The drug absorption rate was found to correlate to the molecular polar surface area (PSA), the hydrogen bonding potential, and the P_app, which indicated that passive diffusion was the predominating mechanism of absorption in the rat lung. In contrast to the intestinal mucosa and the blood-brain barrier, the pulmonary epithelium was shown to be highly permeable to compounds with high PSA (e.g. 479 Ų). Furthermore, a high bioavailability was found for the efflux transporter substrates talinolol (81%) and losartan (92%), which provides functional evidence for a quantitatively less important role for efflux transporters, such as P-glycoprotein, in limiting the absorption of these drugs from the rat lung.
Conclusion: The pulmonary route should be regarded as a potential alternative for the delivery of drugs that are inadequately absorbed after oral administration.

Rating:

Share or cite this content

Citations should be made in the following way:
A. Tronde, B. Nordén, H. Marchner, A. K. Wendel, H. Lennernäs, U. Hultkvist Bengtsson (Lund, Sweden). Pulmonary absorption rate and bioavailability of drugs in vivo in rats: Analysis of structure-absorption relationships. Eur Respir J 2003; 22: Suppl. 45, 162

Member's Comments

No comment yet.

Related content which might interest you: Pharmacokinetic factors affecting airway selectivity of inhaled steroids – role of prodrug conversion and absorption Source: Eur Respir J 2004; 24: Suppl. 48, 347s Year: 2004 Lung absorption half-life of inhaled drugs can be predicted with rat lung slices Source: International Congress 2015 – New models for treating airway diseases Year: 2015 Pharmacokinetic factors affecting airway selectivity of inhaled steroids - role of intracellular esterification Source: Eur Respir J 2001; 18: Suppl. 33, 147s Year: 2001 Acute effects of cisplatin on mucociliary function: In vitro measurements Source: Annual Congress 2010 - Pathology of lung cancer Year: 2010 Interrelationship of pharmacokinetics/pharmacodynamics: antibiotic dosing for the future Source: ISSN=1025-448x, ISBN=1-904097-32-4, page=1 Year: 2004 Novel paradigm for inhaled therapies: simulation of drug pharmacokinetic behaviour and effect of disease Source: Eur Respir J 2003; 22: Suppl. 45, 474s Year: 2003 Systemic bioavailability of inhaled steroids: the importance of appropriate and comparable methodology Source: Eur Respir J 2001; 17: 157-158 Year: 2001 Pharmacokinetic interactions in different combinations of pulmonary arterial hypertension treatment Source: International Congress 2016 – Pulmonary hypertension: the clinic II Year: 2016 Pulmonary and systemic inflammation in a domestic animal model of respiratory chlamydophila psittaci infection: Evaluation of dose-response relationships Source: Annual Congress 2011 - Infection in the immunocompromised host: infrequent aetiologies Year: 2011 Slow particle dissolution may limit lung absorption of inhaled pharmaceuticals in the lungs Source: Eur Respir J 2006; 28: Suppl. 50, 210s Year: 2006 Pharmacokinetics and safety of concomitant macitentan and hormonal contraceptives Source: International Congress 2015 – Pulmonary hypertension: novel clinical insights Year: 2015 In-vivo lung molecular imaging of choline metabolism in a rat model of pulmonary arterial hypertension Source: International Congress 2019 – Pulmonary hypertension with lung diseases and experimental pulmonary hypertension Year: 2019 Measurement of pulmonary structure and function Source: Eur Respir Monogr 2015; 70: 216-232 Year: 2015 A human lung reperfusion model for monitoring the initial pulmonary absorption of drugs from aerosol devices Source: Eur Respir J 2005; 26: Suppl. 49, 125s Year: 2005 Analysis of miRNA profile in circulating microparticles of patients with pulmonary arterial hypertension Source: International Congress 2015 – Pulmonary hypertension: rare and hereditary causes of PAH Year: 2015 Extent of inhaled drug deposition in mouth-throat and pulmonary airways: A novel biophysical modelling approach for inhaled therapeutics Source: International Congress 2015 – New models for treating airway diseases Year: 2015 Gene expression profile of pulmonary inflammation in rat lung induced by nickel oxide nanoparticles following intratracheal instillation Source: International Congress 2015 – Genetics and environmental factors in phenotypes of asthma and COPD Year: 2015 Pulmonary mechanics in a mouse model of emphysema: in vivo and in vitro evaluation Source: Annual Congress 2008 - Inflammatory trigger mechanisms in asthma and COPD Year: 2008 Late Breaking Abstract - Spatial pharmacokinetics of inhaled drugs in human lung – evaluation of regional lung targeting by direct sampling of epithelial lining fluid Source: International Congress 2019 – New towards old therapies in airway diseases Year: 2019 Different tissue accumulation kinetics of ciclesonide-active metabolite and budesonide in mice Source: Eur Respir J 2006; 28: Suppl. 50, 433s Year: 2006