INFLUENCE OF ROUTE OF ADMINISTRATION AND DOSAGE FORM IN THE PHARMACOKINETICS AND BIOAVAILABILITY OF SALBUTAMOL

The present study was carried out to define the pharmacokinetics of sa lbutamol sulfate administered to mongrel dogs in five pharmaceutical f orms via two routes of administration. One pharmaceutical form was adm inistered intravenously (Ventolin(R) i.v.) while the other four were a dministered orally (Ventolin(R): immediate-release formulation, Volmax (R): commercial osmotic pump, SG7 and SG14: sustained-release hydrophi lic matrices developed in our laboratory). We obtained a first-order r elease kinetic of the salbutamol from Ventolin(R) and SG7, whereas a z ero-order release kinetic was observed for SG14 and Volmax(R) formulat ions. Oral bioavailability was 80% and there were neither significant differences (P > 0.05) in terms of the calculation method used (relati on of the areas under the plasma level curve Loo-Riegelman, deconvolut ion) nor in terms of the dosage form (Ventolin(R), Volmax(R), SG7 and SG14). The elimination half-life value of salbutamol was 1.2 h when ad ministered intravenously; this parameter had a value of 3.0 h for the immediate-release formulation and ranged between 5.4 and 7.2 h in the sustained-release formulations when administered orally. These changes in the half-life value of the sustained-release formulations will all ow us to modify the frequency of administration in relation to immedia te-release formulations.