Influence of hypoxia and hypercapnia on the kinetics and hypokaliaemic effect of salbutamol in the rabbit

Abstract

1. The aims were to document the influence of moderate hypoxia or hypercapnia on salbutamol kinetics and its hypokaliaemic effect, following its administration through the intravenous (60μg/kg), intratracheal (60μg/kg), and oral (2400 μg/kg) routes (n = 5). In control animals, PaO₂ was around 85 mmHg and PaCO₂ 20mmHg; in hypoxic animals PaO₂ was around 40mmHg and in the hypercapnic rabbit PaCO₂ was 50mmHg.

2. Following the intravenous administration of salbutamol, the apparent volume of distribution increased two-fold (p < 0.05) in animals with hypoxia and hypercapnia. Consequently, its half life was enhanced (p < 0.05). Given via the trachea, salbutamol bioavailability was decreased by hypoxia.

3. When salbutamol was given orally, hypoxia or hypercapnia increased the area under salbutamol plasma concentration as a function of time (p < 0.05).

4. In control animals, the salbutamol hypokaliaemic effect was greater when administered orally than through the other routes. Compared with control animals, the experimental conditions reduced the hypokaliaemic effect of salbutamol only when given orally.

5. It is concluded that salbutamol kinetics and dynamics can be altered by hypoxia and hypercapnia.