Comparison of the extrapulmonary β2‐adrenoceptor responses and pharmacokinetics of salbutamol given by standard metered dose‐inhaler and modified actuator device
- 1 November 1993
- journal article
- clinical trial
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 36 (5), 445-450
- https://doi.org/10.1111/j.1365-2125.1993.tb00393.x
Abstract
1. Ten healthy subjects were randomised to inhale salbutamol via a standard metered-dose inhaler (MDI), or via a modified metered-dose actuator device (MA). Previously published radiolabelled aerosol data had shown that the MA device produced a lower aerosol velocity, reduced oropharyngeal deposition, but with unchanged pulmonary deposition. 2. Dose-response curves (DRC) were constructed with the following cumulative doses of salbutamol: 200 microg, 600 microg (200 microg + 400 microg), 1400 microg (600microg + 800 microg) ad 2600 microg (1400 + 1200 microg). Dose increments were made every 30 min and measurements of extrapulmonary beta2-adrenoceptor responses were performed 20 min after each dose. In addition, plasma salbutamol concentrations were also measured immediately before and for up to 60 min after the last dose. 3. Baseline values were not significantly different between the two study days for any of the measured parameters. 4. Cmax (ng ml(-1)) for plasma salbutamol (as means and 95% CI for difference between MA and MDI) was: 2.0 (0.3-3.7), P = 0.03. Values for t(max) (min), median and range: MA 5 (5-10) vs MDI 5 (5-10); and AUC 0-60, (ng ml(-1) min, mean and 95% CI for difference between MA and MDI): 69 (-5-143), were not significantly different between the two devices. 5. There was a significant (P < 0.01) left shift in the DRC with the MA device compared with the MDI, for hypokalaemic, finger tremor, chronotropic and electrocardiographic (Twave, Q-Tc) responses to salbutamol. Values for the hypokalaemic response (mmol l(-1)) at 2600 microg were (as change from baseline, means and 95% CI for difference between MA and MDI): 0.23 (0.10-0.36). 6. Thus, the MA device produced greater systemic absorption of salbutamol, and associated extrapulmonary beta2-adrenoceptor responses compared with a standard MDI. These results, therefore, suggest that data from radiolabelled aerosol deposition studies may not predict the systemic absorption of inhaled beta2-adrenoceptor agonists.Keywords
This publication has 25 references indexed in Scilit:
- AN ANALYSIS OF THE TIME‐RELATIONS OF ELECTROCARDIOGRAMS.Annals of Noninvasive Electrocardiology, 1997
- Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.Thorax, 1993
- Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline.Thorax, 1992
- Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler.Thorax, 1991
- Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids?Thorax, 1990
- Decreased adreno‐cortical suppression utilizing the Nebuhaler for inhalation of steroid aerosolsClinical and Experimental Allergy, 1987
- The efficacy of drug delivery by a pear-shaped spacer and metered dose inhalerRespiratory Medicine, 1984
- Improvement of pressurised aerosol deposition with Nebuhaler spacer device.Thorax, 1984
- Comparison of three techniques of inhalation on the airway response to terbutaline.Thorax, 1983
- Deposition of pressurised aerosols in the human respiratory tract.Thorax, 1980