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 hypercapnia on salbutamol kinetics and its hypokaliaemic effect, following its administration through the intravenous (60 micrograms/kg), intratracheal (60 micrograms/kg), and oral (2400 micrograms/kg) routes (n = 5). In control animals, PaO2 was around 85 mmHg and PaCO2 20 mmHg; in hypoxic animals PaO2 was around 40 mmHg and in the hypercapnic rabbit PaCO2 was 50 mmHg. 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.
Perreault
S
S
Département de Pharmacologie, Université de Montréal, Québec, Canada.
Saunier
C
C
Ong
H
H
Du Souich
P
P
D000284:Administration, Oral; D000420:Albuterol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D006207:Half-Life; D006935:Hypercapnia / Q000097:blood*; D000860:Hypoxia / Q000097:blood*; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000097:blood*; D011817:Rabbits; D014132:Trachea / Q000187:drug effects
D000420:Albuterol; D011188:Potassium