Pharmacodynamic methods for investigating antiasthma drugs in healthy volunteers

Abstract

The investigation of bronchoactive drugs in healthy volunteers may be divided into studies on the drug effects on basal airway calibre, the effects on induced bronchoconstriction and the examination of the pharmacokinetic and side effect profile of new chemical entities. In the studies presented in this paper, whole body plethysmography was used to assess the pharmacological activity of three new development compounds. In the first example, bronchodilatation was measured after administration of an anticholinergic drug. In two further examples, the bronchial effects were studied in asthma models in which an increase in airflow resistance was produced using inhaled methacholine and platelet activating factor (PAF). The method applied in these tests allowed the antagonistic effects of drugs on the constrictor effect of individual agents to be followed. Antiasthmatic drugs can also have a systemic effect on different physiological and biochemical parameters. These parameters can be applied as useful tools in the determination of the pharmacological activity of a given drug, irrespective of the conventional methods used to evaluate the efficacy of bronchodilators by the degree of bronchial muscular relaxation. A complex nonbronchial model is shown in order to demonstrate how it is possible to identify the pharmacologically effective dose of a new beta 2-adrenoceptor agonist.