SALBUTAMOL DISPOSITION AND DYNAMICS IN CONSCIOUS RABBITS - INFLUENCE OF THE ROUTE OF ADMINISTRATION AND OF THE DOSE

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 mug/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 mug/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 mug/kg), total plasma clearance was 82 +/- 5 ml/min per kg, apparent volume of distribution was 5.0 +/- 0.5 l/kg, and terminal half-life was 41 +/- 2 min. Similar values were estimated when 120 mug/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80 +/- 0.19, 0.48 +/- 0.22, and 0.78 +/- 0.46 mmol/l, and for the second group, maximal decrement was 1.31 +/- 0.37, 0.70 +/- 0.24, and 0.84 +/- 0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentration. The hypokaliemic effect was dependent upon the route, e.g., po > it > iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effects is modulated by the dose and the route of administration.