Bronchodilating Effect and Side Effects of BetaaAdrenoceptor Stimulants by Different Modes of Administration (Tablets, Metered Aerosol, and Combinations Thereof) A Study with Salbutamol in Asthmatics13
SVEN LARSSON AND NILS SVEDMYR
SUMMARY. Effects and side effects of an adrenergic /30-stimulant (salbutamol) given by mouth and by inhalation from a metered aerosol were compared. Cumulative dose-response curves for both routes of administration concerning 1-sec forced expiratory volume, forced vital capacity, heart rate, blood pressure, and tremor were constructed. Tremor was found to be the dose-limiting side effect with both modes of administration. The metered aerosol in doses as large as 0.6 mg was shown to produce a greater increase in the 1-sec forced expiratory volume, with fewer side effects than could be achieved with tolerable doses of salbutamol by mouth. An oral dose of 6 mg is probably the maximal tolerable dose in most cases. Oral treatment seems to have a better effect than inhalation treatment on the forced vital capacity at the same effect on 1-sec forced expiratory volume, possibly due to a better effect on small peripheral airways. The effect of combining different oral doses of salbutamol with inhaled salbutamol was also studied. A very good additional effect of inhalations given after 4 and 6 mg by mouth was shown.
Introduction Long-term maintenance therapy of asthma with /3 2 -adrenoceptor stimulants is commonly practiced in Europe. These drugs can be administered in several ways. Tablets or the metered(Received in original form March 30, 1977 and in revised form August 8,1977) 1 From the Department of Clinical Pharmacology and Lung Clinic, University of Goteborg, Goteborg, Sweden. 2 Supported by grants from the Swedish National . . . TT ^. r Association against Heart and Chest Diseases, from the Swedish Society for Medical Research, and from the Goteborg Medical Society. 3 Requests for reprints should be addressed to Sven Larsson, M.D., Renstromska Hospital, S-402 60 Goteborg, Sweden.
dose aerosol are almost exclusively used for longterm treatment. Sometimes combinations of tablets and inhalations are given, In only a few studies have the effects of /3-stimulants given by different modes of administration been studied (1-5). T h e prime object of these studies, however, was to describe a certain pstimulant and not to compare various modes of administration. Only low doses were given, a n d no objective registration of tremor, the most c o m m o n s i d e effect (6), was made. Inhalation infusion of terbutaline were an(j j n t r a v e n o u s , , ~, . . , * /n\ u compared by T h i n n g e r and cSvedmyr (7) by r J ° ' . . p construction of dose-response curves. Inhalation w a s f o u n d to produce fewer effects and better bronchodilation than parenteral treatment. Probably the same difference will also exist for tablets and inhalation.
AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME 116, 1977
861
862
LARSSON AND SVEDMYR CO
In the present study, bronchodilating effect and side effects of oral and inhaled salbutamol were compared after construction of cumulative dose-response curves in asthmatics. Combinations of tablets and inhalations from a metereddose aerosol at different dosages were also studied.
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SVEN LARSSON AND NILS SVEDMYR
SUMMARY. Effects and side effects of an adrenergic /30-stimulant (salbutamol) given by mouth and by inhalation from a metered aerosol were compared. Cumulative dose-response curves for both routes of administration concerning 1-sec forced expiratory volume, forced vital capacity, heart rate, blood pressure, and tremor were constructed. Tremor was found to be the dose-limiting side effect with both modes of administration. The metered aerosol in doses as large as 0.6 mg was shown to produce a greater increase in the 1-sec forced expiratory volume, with fewer side effects than could be achieved with tolerable doses of salbutamol by mouth. An oral dose of 6 mg is probably the maximal tolerable dose in most cases. Oral treatment seems to have a better effect than inhalation treatment on the forced vital capacity at the same effect on 1-sec forced expiratory volume, possibly due to a better effect on small peripheral airways. The effect of combining different oral doses of salbutamol with inhaled salbutamol was also studied. A very good additional effect of inhalations given after 4 and 6 mg by mouth was shown.
Introduction Long-term maintenance therapy of asthma with /3 2 -adrenoceptor stimulants is commonly practiced in Europe. These drugs can be administered in several ways. Tablets or the metered(Received in original form March 30, 1977 and in revised form August 8,1977) 1 From the Department of Clinical Pharmacology and Lung Clinic, University of Goteborg, Goteborg, Sweden. 2 Supported by grants from the Swedish National . . . TT ^. r Association against Heart and Chest Diseases, from the Swedish Society for Medical Research, and from the Goteborg Medical Society. 3 Requests for reprints should be addressed to Sven Larsson, M.D., Renstromska Hospital, S-402 60 Goteborg, Sweden.
dose aerosol are almost exclusively used for longterm treatment. Sometimes combinations of tablets and inhalations are given, In only a few studies have the effects of /3-stimulants given by different modes of administration been studied (1-5). T h e prime object of these studies, however, was to describe a certain pstimulant and not to compare various modes of administration. Only low doses were given, a n d no objective registration of tremor, the most c o m m o n s i d e effect (6), was made. Inhalation infusion of terbutaline were an(j j n t r a v e n o u s , , ~, . . , * /n\ u compared by T h i n n g e r and cSvedmyr (7) by r J ° ' . . p construction of dose-response curves. Inhalation w a s f o u n d to produce fewer effects and better bronchodilation than parenteral treatment. Probably the same difference will also exist for tablets and inhalation.
AMERICAN REVIEW OF RESPIRATORY DISEASE, VOLUME 116, 1977
861
862
LARSSON AND SVEDMYR CO
In the present study, bronchodilating effect and side effects of oral and inhaled salbutamol were compared after construction of cumulative dose-response curves in asthmatics. Combinations of tablets and inhalations from a metereddose aerosol at different dosages were also studied.
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