Abstract
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 μg/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 μg/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 μg/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 μg/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 concentrations. 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 effect is modulated by the dose and the route of administration.
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Abbreviations
- AUC :
-
Area under salbutamol plasma concentration-time curve
- clINT :
-
Salbutamol intrinsic clearance
- clT :
-
Salbutamol total plasma clearance
- cMAX :
-
Salbutamol maximal plasma concentration
- F :
-
Fraction of the dose of salbutamol reaching the systemic circulation
- iv:
-
Intravenous route of administration
- it:
-
Intratracheal route of administration
- po:
-
Oral route of administration
- Varea :
-
Salbutamol apparent volume of distribution
- T 12 :
-
Salbutamol half-life of the terminal phase
- tMAX :
-
Time to observe the maximal decrease in plasma potassium
- eMAX :
-
Predicted maximal effect of salbutamol
- EC50 :
-
Concentration of salbutamol eliciting 50% of eMAX
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Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.
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Perreault, S., Ong, H. & du Souich, P. Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose. Journal of Pharmacokinetics and Biopharmaceutics 20, 461–476 (1992). https://doi.org/10.1007/BF01061466
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DOI: https://doi.org/10.1007/BF01061466