No pharmacokinetic interactions were observed between budesonide and formoterol. Budesonide dose variation in budesonide/formoterol pMDI did not affect formoterol exposure. Steady state budesonide/formoterol pMDI dose-doubling yielded proportional increases in budesonide and formoterol exposure.
ObjectivesTo evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children.
MethodsTwenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis ® ) 4.5 m g (F4.5) or terbutaline (Bricanyl ® ) 500 m g (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler ® ) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency.
ResultsFormoterol and terbutaline had significant b 2 -adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l -1 on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 ¥ F4.5 and 2.70 (CI: 2.61-2.78) mmol l -1 after 10 ¥ T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 ¥ F4.5 and 470 (CI: 463-476) ms after 10 ¥ T500. Estimates of relative dose potency indicated that F4.5 m g had the same systemic activity as the clinically less effective dose of 250 m g terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 m g formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h.
ConclusionsMultiple inhalations over 2.5 h of formoterol (4.5 m g) via Turbuhaler ® are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 m g) in children with asthma.
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