caa a22 4500 475818881 CHVBK 20180406123817.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s002280000160 doi (NATIONALLICENCE)springer-10.1007/s002280000160 Relative systemic dose potency and tolerability of inhaled formoterol and salbutamol in healthy subjects and asthmatics [Elektronische Daten] [J. Rosenborg, T. Bengtsson, P. Larsson, A. Blomgren, G. Persson, J. Lötvall] Objectives: To compare the relative systemic dose potency and tolerability of inhaled formoterol and salbutamol and to describe elimination of formoterol, particularly any enantioselectivity. Methods: Twelve healthy subjects, aged 18-28 years, completed three open study days, and eleven asthmatic patients, aged 20-56 years, completed four double-blind study days in randomised, placebo-controlled and crossover fashions. The healthy subjects inhaled 13.5 + 13.5 + 27 μg formoterol (Oxis) via Turbuhaler and 300 + 300 + 600 μg salbutamol (Ventoline) via a pressurised metered dose inhaler (pMDI). The asthmatics, being on formoterol 9 μg twice daily via Turbuhaler during the study, inhaled the same single doses as the healthy subjects plus 900 + 900 + 1800 μg salbutamol via pMDI. Doses were given cumulatively 30 min apart on separate study days. Placebo was a day of no treatment in the healthy subjects. Double dummies were used for the asthmatics. Cardiovascular and metabolic effects were evaluated. Elimination of formoterol was addressed in the healthy subjects. Results: Formoterol was estimated to be 28-109 times as potent as salbutamol, depending on the systemic effect variable. The duration of systemic action seemed to differ marginally at approximately equieffective doses of formoterol and salbutamol. Systemic effects were well tolerated and tended to be more pronounced in the healthy subjects than in the asthmatic patients. The half-life of the pharmacologically more active (R;R)-formoterol was longer than that of (S;S)-formoterol. Conclusions: Systemically, formoterol was shown to be 28-109 times as potent as salbutamol. Equieffective doses seemed to have a similar duration of effect. Formoterol and salbutamol were well tolerated by healthy subjects up to the tested total doses of 54 μg and 1200 μg, respectively, and by asthmatic patients up to the tested total doses of 54 μg and 3600 μg, respectively. Elimination of formoterol was enantioselective. Springer-Verlag Berlin Heidelberg, 2000 Key words Formoterol nationallicence Salbutamol nationallicence Tolerability nationallicence Rosenborg J. Experimental Medicine, AstraZeneca R&D Lund, S-221 87 Lund, Sweden e-mail: Johan.Rosenborg@astrazeneca.com, SE aut Bengtsson T. Clinical Science, AstraZeneca R&D Lund, Sweden, SE aut Larsson P. Clinical Science, AstraZeneca R&D Lund, Sweden, SE aut Blomgren A. Pharmacokinetics and Bioanalysis, AstraZeneca R&D Lund, Sweden, SE aut Persson G. Department of Pulmonary Medicine, University of Lund, Sweden, SE aut Lötvall J. Clinical Pharmacology, University of Göteborg, Sweden, SE aut https://doi.org/10.1007/s002280000160 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000160 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rosenborg J. Experimental Medicine, AstraZeneca R&D Lund, S-221 87 Lund, Sweden e-mail: Johan.Rosenborg@astrazeneca.com, SE aut NATIONALLICENCE 700 1- Bengtsson T. Clinical Science, AstraZeneca R&D Lund, Sweden, SE aut NATIONALLICENCE 700 1- Larsson P. Clinical Science, AstraZeneca R&D Lund, Sweden, SE aut NATIONALLICENCE 700 1- Blomgren A. Pharmacokinetics and Bioanalysis, AstraZeneca R&D Lund, Sweden, SE aut NATIONALLICENCE 700 1- Persson G. Department of Pulmonary Medicine, University of Lund, Sweden, SE aut NATIONALLICENCE 700 1- Lötvall J. Clinical Pharmacology, University of Göteborg, Sweden, SE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer