INFLUENCE OF HYPOXIA AND HYPERCAPNIA ON THE KINETICS AND HYPOKALIAEMIC EFFECT OF SALBUTAMOL IN THE RABBIT

1. The aims were to document the influence of moderate hypoxia or hype rcapnia on salbutamol kinetics and its hypokaliaemic effect, following its administration through the intravenous (60 mu g/kg), intratrachea l (60 mu g/kg), and oral (2400 mu g/kg) routes (n = 5). In control ani mals, PaO2 was around 85 mmHg and PaCO2 20 mmHg; in hypoxic animals Pa O2 was around 40 mmHg and in the hypercapnic rabbit PaCO2 was 50 mmHg. 2. Following the intravenous administration of salbutamol, the appare nt volume of distribution increased two-fold (p < 0.05) in animals wit h hypoxia and hypercapnia. Consequently, its half life was enhanced (p < 0.05). Given via the trachea, salbutamol bioavailability was decrea sed by hypoxia. 3. When salbutamol was given orally, hypoxia or hyperc apnia increased the area under salbutamol plasma concentration as a fu nction of time (p < 0.05). 4. In control animals, the salbutamol hypok aliaemic effect was greater when administered orally than through the other routes. Compared with control animals, the experimental conditio ns reduced the hypokaliaemic effect of salbutamol only when given oral ly. 5. It is concluded that salbutamol kinetics and dynamics can be al tered by hypoxia and hypercapnia.