Comparative pharmacology, bioavailability, pharmacokinetics, and pharmacodynamics of inhaled glucocorticosteroids

Immunol Allergy Clin North Am. 2005 Aug;25(3):469-88. doi: 10.1016/j.iac.2005.05.004.

Abstract

A comparison of the pharmacodynamics and pharmacokinetics of inhaled corticosteroids is necessary for their assessment. A good knowledge of these two aspects allows the optimization of efficacy and safety.The currently available inhaled corticosteroids already show some of the desired PK/PD parameters. The local adverse effects are decreased as soon as the inhaled corticosteroid is administered as an inactive prodrug or shows a bet-ter lung deposition. HFA-MDI beclomethasone dipropionate (BDP) and ciclesonide are two agents that illustrate this. Low oral bioavailability, rapid systemic clearance, and high plasma protein binding can minimize systemic adverse effects. Mometasone furoate, ciclesonide, and fluticasone propionate possess those characteristics. The pulmonary efficacy is maximized by high lung deposition and long pulmonary residence times. This effect can be achieved by slow dissolution in the lungs, as is the case for fluticasone propionate or lipid conjugation and has been shown for budesonide and ciclesonide. Furthermore, the lung deposition depends on the inhalation device, the particle size, and the inhalation technique. Therefore,improvement in the design of MDIs, DPIs, and nebulizers, and the development of more effective drug particles will lead to an optimized pulmonary targeting. Much progress has been made in the treatment of asthma. The available inhaled corticosteroids show a high safety profile and a good pulmonary selectivity. Development of newer compounds showed that improvement is possible as the result of a complete understanding of the PK/PD concepts. However,the introduction of further improved formulations with a better efficacy/safety profile will be difficult and protracted because the existing drugs are already highly efficient.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Administration, Inhalation
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Asthma / drug therapy
  • Asthma / metabolism
  • Biological Availability
  • Drug Design
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacokinetics*
  • Glucocorticoids / pharmacology*
  • Half-Life
  • Humans
  • Lung / metabolism
  • Nebulizers and Vaporizers
  • Particle Size
  • Prodrugs / administration & dosage
  • Prodrugs / pharmacokinetics
  • Prodrugs / pharmacology
  • Protein Binding
  • Receptors, Glucocorticoid / drug effects
  • Receptors, Glucocorticoid / metabolism

Substances

  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Prodrugs
  • Receptors, Glucocorticoid