Onset and duration of action of single doses of formoterol inhaled via Turbuhaler®

The aim of the study was to investigate the time of onset and the duration of the bronchodilating effect of different doses of formoterol administered via Tulbuhaler(R) in patients with moderate asthma. Thirty-one patients (five women) with a mean forced expiratory volume in s (FEV1) of 1.97 +/- 0.541 and a mean reversibility of 31 +/- 14% of baseline were included in this double-blind. randomized. placebo-controlled and cross-over study. The patients inhaled single doses of placebo, i.e. 6, 12, 24, or 48 mu g formoterol fumarate, on 5 separate days. Serial measurements of specific airways conductance (SGaw) and FEV1 were performed at regular time intervals for 12 h. The majority of the patients had at least a 50% increase in SGAW within 1-4 min after administration of all active treatments. The maximum increase in FEV1 over placebo was dose-dependent: 12% (6 mu g), 18% (12 mu g), 19% (24 mu g), and 26% (48 mu g) (P<0.001). Twelve hours after administration of 6. 12, 24, and 48 mu g formoterol, the mean increase in FEV1 was still 7%, 15%, 18% and 27%, respectively, above the value following placebo. Headache was the most frequently reported adverse event in all treatments including placebo. After inhalation of 48 mu g, three patients experienced mild tremor lasting for less than 1 h; likewise, one patient experienced the same event for 3 h after placebo. Formoterol administered via Turbuhaler(R) gave a rapid and dose-related bronchodilating effect lasting for 12 h and was well tolerated

The inhalation device influences lung deposition and bronchodilating effect of terbutaline

The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV(1) 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhale(R) (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV(1) increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV(1) increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect