Assessment of different methods of inhalation from salbutamol metered dose inhalers by urinary drug excretion and methacholine challenge

Abstract

Methods to determine the lung delivery of inhaled bronchodilators from metered dose inhalers include urinary drug excretion 30 min post inhalation and methacholine challenge (PD20). We have compared these two methods to differentiate lung delivery of salbutamol from metered dose inhalers using different inhalation methods. In phase 1 of the study, on randomized study days, 12 mild asthmatics inhaled placebo, one and two 100 microg salbutamol doses from a breath actuated metered dose inhaler, in randomized fashion on different days. In phase 2, they inhaled one 100 microg salbutamol dose from a metered dose inhaler using a SLOW (20 l min(-1)) and a FAST (60 l min(-1)) inhalation technique and a slow inhalation delayed until after they had inhaled for 5 s (LATE). Urinary excretion of salbutamol (0-30 min) and PD20 were measured after each dose. Following placebo, one and two 100 microg salbutamol doses, the geometric mean for PD20 was 0.10, 0.41 and 0.86 mg respectively and the mean (SD) urinary drug excretion after one and two doses was 2.25 (0.65) and 5.37 (1.36) microg, respectively. After SLOW, FAST and LATE inhalations the geometric mean for PD20 was 0.50, 0.40 and 0.42 mg, respectively, and mean (SD) salbutamol excretion was 2.67 (0.84), 1.90 (0.70) and 2.72 (0.67) microg, respectively. Only the amount of drug excreted during the FAST compared with the SLOW and LATE inhalations showed a statistical difference (95% confidence interval on the difference 0.12, 1.54 and 0.06, 1.59 microg, respectively). Urinary salbutamol excretion but not PD20 showed differences between the inhalation methods used. When using a metered dose inhaler slow inhalation is better and co-ordination is not essential if the patient is inhaling when they actuate a dose of the drug.