PLASMA-CONCENTRATIONS AND EFFECTS OF SALBUTAMOL ADMINISTERED ORALLY TO PATIENTS WITH CYSTIC-FIBROSIS

1 To test whether cystic fibrosis (CF) altered the kinetics and dynamics of oral salbutamol, 11 patients with CF (19-33 years old; five females; FEV(1): 37 +/- 12% of predicted value) and 10 healthy volunteers (20-41 years old; five females; FEV(1): 99 +/- 14% of predicted value) received orally 4 mg salbutamol. 2 The estimated pharmacokinetic parameters of salbutamol in patients with CF were identical to those in healthy subjects. For instance, peak plasma concentrations of salbutamol were 10.5 +/- 2.6 (mean +/- s.d.) and 10.2 +/- 2.9 ng ml(-1) (NS), and the area under salbutamol plasma concentrations as a function of time (AUC (0.7 h)) was 43.0 +/- 9.3 ng ml(-1) h and 43.3 +/- 12.7 ng ml(-1) h (NS) in CF patients and in healthy subjects, respectively. Since on a mg kg(-1) dose basis, CF patients received a dose 28% greater than healthy subjects, this lack of differences implies a decrease in the amount of salbutamol absorbed, or alternatively, an increase in both clearance and volume of distribution of salbutamol. 3 Salbutamol did not elicit bronchodilation in CF patients, but increased heart rate from 77 +/- 2 to 103 +/- 3 beats min(-1) (P < 0.05). 4 Salbutamol decreased plasma potassium concentrations from 4.5 +/- 0.1 to 3.8 +/- 0.1 mmol l(-1) in the CF group (P < 0.05) and from 4.1 +/- 0.2 to 3.4 +/- 0.1 mmol l(-1) in the controls (P < 0.05). Plasma glucose concentrations were increased from 5.4 +/- 0.4 to 6.8 +/- 0.5 mmol l(-1) in CF patients, and from 5.1 +/- 0.2 to 6.3 +/- 0.4 mmol l(-1) (P < 0.05) in the controls. 5 The results suggest that in CF there are changes in the kinetics of salbutamol.