Lung deposition and protective effect of terbutaline delivered from pressurized metered-dose inhalers and the turbuhaler in asthmatic individuals

We investigated the relationship between pulmonary deposition of terbutalin e and bronchoprotection against methacholine and histamine with the Turbuha ler (AstraZeneca, Lund, Sweden) and a pressurized metered dose inhaler (pMD I) in 13 asthmatic patients. The study was done with a randomized, double b lind, double dummy, and crossover design. On different days, the provocativ e concentration. of histamine causing a 20% decrease in FEV1 (PC20 histamin e) and PC20 methacholine were determined before and at 1.5, 3, and 6 h afte r inhalation of 0.25 or 0.5 mg of terbutaline sulfate. The Turbuhaler deliv ered significantly more drug than did the pMDI (% of the nominal metered do se and 95% confidence interval): 20.8% (16.4 to 26.6%) and 16.9% (13.2 to 2 1.7%) versus 4.8% (3.8 to 6.1%) and 7.4% (5.8 to 9.5%), respectively. Avera ge protection against histamine over 6 h was 0.66 (95% CI: 0.45 to 0.87) do ubling concentrations (DC) after inhalation of 0.25 mg and 1.08 (95% Cl: 0. 87 to 1.29) DC after 0.5 mg terbutaline via pMDI, and 1.07 (95% Cl: 0.87 to 1.29) DC after 0.25 mg and 1.24 (95% Cl: 1.03 to 1.45) DC after 0.50 mg vi a Turbuhaler. Protection against methacholine was also dose- and device-dep endent. The dose needed to obtain the same pulmonary deposition with the pM DI was 3.14 times greater than with the Turbuhaler, and that needed for the same protective effect was. 2.1 and 3.2 times greater for histamine and me thacholine, respectively. We conclude that pulmonary deposition of terbutal ine was predictive of the clinical response.