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 terbutaline and bronchoprotection against methacholine and histamine with the Turbuhaler (AstraZeneca, Lund, Sweden) and a pressurized metered dose inhaler (pMDI) in 13 asthmatic patients. The study was done with a randomized, double blind, double dummy, and crossover design. On different days, the provocative concentration. of histamine causing a 20% decrease in FEV1 (PC20 histamine) and PC20 methacholine were determined before and at 1.5, 3, and 6 h after inhalation of 0.25 or 0.5 mg of terbutaline sulfate. The Turbuhaler delivered significantly more drug than did the pMDI (% of the nominal metered dose and 95% confidence interval): 20.8% (16.4 to 26.6%) and 16.9% (13.2 to 21.7%) versus 4.8% (3.8 to 6.1%) and 7.4% (5.8 to 9.5%), respectively. Average protection against histamine over 6 h was 0.66 (95% CI: 0.45 to 0.87) doubling 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 via Turbuhaler. Protection against methacholine was also dose- and device-dependent. The dose needed to obtain the same pulmonary deposition with the pMDI 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 methacholine, respectively. We conclude that pulmonary deposition of terbutaline was predictive of the clinical response.