title: Speed of onset of bronchodilator response to salbutamol inhaled via different devices in asthmatics: a bioassay based on functional antagonism.
abstract: OBJECTIVE
  To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction.
  
  
  METHODS
  Eighteen patients inhaled methacholine (MCh) until FEV(1) decreased by 35% of control. Following administration of placebo, 200 microg salbutamol or 400 microg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV(1) and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method.
  
  
  RESULTS
  For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV(1) and volume-adjusted mid-expiratory flow similar to those obtained with 200 microg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) microg, 395 (95% CI 388, 404) microg and 404 (95% CI 393, 415) microg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07).
  
  
  CONCLUSIONS
  Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus.
authors.affiliation: Dipartimento di Area Critica Medico Chirurgica, Unità Funzionale di Medicina Respiratoria, Università degli Studi di Firenze, Italia. f.lavorini@dac.unifi.it
authors.forename: Federico
authors.initials: F
authors.lastname: Lavorini
authors.forename: Pietro
authors.initials: P
authors.lastname: Geri
authors.forename: Laura
authors.initials: L
authors.lastname: Mariani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marmai
authors.forename: Nazzarena Maria
authors.initials: NM
authors.lastname: Maluccio
authors.forename: Massimo
authors.initials: M
authors.lastname: Pistolesi
authors.forename: Giovanni A
authors.initials: GA
authors.lastname: Fontana
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D014797:Vital Capacity / Q000502:physiology
chemical_list: D001993:Bronchodilator Agents; D000420:Albuterol