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Titolo:
Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects
Autore:
Guhan, AR; Cooper, S; Oborne, J; Lewis, S; Bennett, J; Tattersfield, AE;
Indirizzi:
City Hosp, Sch Med & Surg Sci, Div Resp Med, Nottingham NG5 1PB, England City Hosp Nottingham England NG5 1PB sp Med, Nottingham NG5 1PB, England
Titolo Testata:
THORAX
fascicolo: 8, volume: 55, anno: 2000,
pagine: 650 - 656
SICI:
0040-6376(200008)55:8<650:SEOFAS>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-2-ADRENOCEPTOR AGONIST; INHALED FORMOTEROL; ASTHMATIC-PATIENTS; BETA-2 AGONIST; SALBUTAMOL; DURATION; TOLERABILITY; INHALATION; ALBUTEROL;
Keywords:
beta(2) agonist; formoterol; salmeterol; systemic effects; dose response;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Tattersfield, AE City Hosp, Sch Med & Surg Sci, Div Resp Med, Clin Sci Bldg,Hucknall Rd, Nottingham NG5 1PB, England City Hosp Clin Sci Bldg,HucknallRd Nottingham England NG5 1PB
Citazione:
A.R. Guhan et al., "Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects", THORAX, 55(8), 2000, pp. 650-656

Abstract

Background-The main adverse effects of inhaled long acting beta(2) agonists relate to their systemic activity. The systemic effects seen over eight hours after inhalation of three doses of salmeterol and formoterol were therefore compared in normal subjects. Methods-A double blind, randomised, crossover study was carried out in 16 healthy subjects who inhaled formoterol 24, 48 and 96 mu g (via Turbuhaler(R)), salmeterol 100, 200 and 400 mu g (via Diskhaler(R)), or placebo on separate days. Heart rate, systolic and diastolic blood pressure, and plasma potassium and glucose concentrations were measured for eight hours followingeach drug and mean values were used to plot the time course of change after each dose. Mean maximum (or minimum) absolute values were used to construct dose-response curves to calculate the relative dose potency of the two drugs. Lunch was taken after the four hour readings and, since this caused additional changes to the main outcome measures, data from the first four hours are also presented in a post hoc analysis. Results-Both salmeterol and formoterol caused an early dose dependent increase in heart rate and glucose concentrations and a fall in diastolic bloodpressure and plasma potassium concentration; formoterol also caused an early increase in systolic blood pressure. The cardiovascular effects occurredmore rapidly than the metabolic effects and the response to formoterol wasfaster than that of salmeterol, apart from the glycaemic response. The effects of salmeterol were slightly more prolonged than those of formoterol, although some dose related effects were apparent at eight hours with both drugs. The relative dose potency for formoterol compared with salmeterol at four and eight hours for the different end points excluding systolic blood pressure ranged from 1.6 to 7.0 after adjusting for baseline values. Relative dose potencies (95% CI) for maximum heart rate and plasma potassium concentrations were 4.1 (3.0 to 5.6) and 5.8 (4.1 to 8.6) over four hours and 2.4 (1.2 to 3.8) and 3.0 (1.2 to 5.7) over eight hours. Conclusions-Formoterol and salmeterol cause dose related changes in heart rate, diastolic blood pressure, and plasma glucose and potassium concentrations. Formoterol has a more rapid onset for most end points whereas salmeterol has slightly more prolonged activity Both drugs have a relatively modest therapeutic window. The relative dose potencies of the two drugs for the main end points were similar to the fourfold difference in recommended doses. Some differences in the pharmacological profile of the two drugs emergedand are as yet unexplained.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/21 alle ore 18:30:19