PK PD ANALYSIS OF ALBUTEROL ACTION - APPLICATION TO A COMPARATIVE-ASSESSMENT OF BETA(2)-ADRENERGIC DRUGS/

Lung function (forced expiratory volume during one second, FEV1), hear t rate and albuterol (salbutamol) plasma levels were recorded in 11 su bjects with mild intermittent asthma after oral administration of albu terol. Pulmonary and cardiovascular data of this and other studies wer e directly linked to the corresponding plasma concentrations via an Em ax relationship, resulting in EC50 values for the heart rate and lung function of 18 and 5 ng/ml, respectively. An integrated PK/PD analysis of these and previously reported data on fenoterol and terbutaline re sulted in the following clinically relevant conclusions: (I) Albuterol and terbutaline are about 25-fold less active at the site of action t han fenoterol; the three drugs show similar cardiac to bronchopulmonar y selectivities. (II) The relative clinical activities after infusion decline in the following order: fenoterol (8) > terbutaline (2) > albu terol (1). (III) Significant differences in the oral bioavailability c ause an opposite rank order after oral administration. (IV) The model related the higher systematic side effects after inhalation of fenoter ol to an over-dosing problem.