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Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years‐old than cumulative high doses of inhaled terbutaline
Author(s) -
Kaae Rikke,
Agertoft Lone,
Pedersen Sören,
Nordvall S Lennart,
Pedroletti Christophe,
Bengtsson Thomas,
JohannesHellberg Ingegerd,
Rosenborg Johan
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2004.02178.x
Subject(s) - terbutaline , tolerability , formoterol , medicine , dry powder inhaler , crossover study , asthma , cumulative dose , anesthesia , confidence interval , blood pressure , bronchodilator , adverse effect , inhaler , budesonide , alternative medicine , pathology , placebo
Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years‐old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis ® ) 4.5 µg (F4.5) or terbutaline (Bricanyl ® ) 500 µg (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. Results Formoterol and terbutaline had significant β 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 µg had the same systemic activity as the clinically less effective dose of 250 µg 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 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Conclusions Multiple inhalations over 2.5 h of formoterol (4.5 µg) 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 µg) in children with asthma.