title: Pharmacokinetics and systemic beta2-adrenoceptor-mediated responses to inhaled salbutamol.
abstract: OBJECTIVE
  To examine whether systemic beta2-adrenoceptor responses, such as tachycardia, tremor and hypokalaemia, can be used as a surrogate for the 20 min pharmacokinetic profile of inhaled salbutamol.
  
  
  METHODS
  A retrospective analysis of eight separate published studies in healthy volunteers was performed, each with an identical protocol evaluating the early lung absorption profile of a nominal 1200 microg dose of salbutamol given by different inhaler devices. Peak postural finger tremor, plasma potassium and heart rate were assessed.
  
  
  RESULTS
  We found the maximum (Cmax) and average (Cav) plasma concentrations of salbutamol to be correlated (P < 0.0001) to change in plasma potassium (Cmax r = 0.904; Cav r = 0.899) and tremor (Cmax r = 0.875; Cav r = 0.857). No significant correlations existed between change in heart rate and Cmax (r = 0.425) or Cav (r = 0.415).
  
  
  CONCLUSIONS
  Systemic beta2-adrenoceptor responses, in particular hypokalaemia and tremor, but not heart rate, appear to be good surrogates for evaluating the lung delivery of inhaled salbutamol. Consequently it is suggested that potassium or tremor responses may be used to evaluate the relative lung delivery of salbutamol from different inhaler devices.
authors.affiliation: Asthma and Allergy Research Group, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Fowler
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000378:metabolism*; D011188:Potassium / Q000097:blood; D012044:Regression Analysis; D014202:Tremor / Q000139:chemically induced
chemical_list: D000318:Adrenergic beta-Agonists; D000420:Albuterol; D011188:Potassium