title: Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective.
abstract: Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High lung deposition/targeting, high receptor binding, longer pulmonary retention, and high lipid conjugation are among the pharmacokinetic parameters to be considered for improved efficacy of the compound. Low or negligible oral bioavailability, small particle size and inactive drug at the oropharynx, high plasma protein binding, rapid metabolism, high clearance, and lower systemic concentrations are associated with low risks for adverse effects. Inhaled glucocorticoid potency is enhanced by solution inhalers, which result in higher pulmonary deposition and minimize local adverse effects. These properties, among others, determine the efficacy and safety of inhaled glucocorticoids. Currently available inhaled glucocorticoids do not provide the complete pharmacokinetic/pharmacodynamic parameters to optimize RBV, leaving room for improvement in the development of future agents.
authors.affiliation: Aventis Pharmaceuticals, Bridgewater, NJ 08807-0800, USA.
authors.forename: Shashank
authors.initials: S
authors.lastname: Rohatagi
authors.forename: Sireesh
authors.initials: S
authors.lastname: Appajosyula
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Stanley
authors.initials: S
authors.lastname: Szefler
authors.forename: Ruediger
authors.initials: R
authors.lastname: Nave
authors.forename: Karl
authors.initials: K
authors.lastname: Zech
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
mesh_terms: D000280:Administration, Inhalation; D001249:Asthma / Q000188:drug therapy*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D005938:Glucocorticoids / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018570:Risk Assessment
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid