title: Inhalation rate of sodium cromoglycate determines plasma pharmacokinetics and protection against AMP-induced bronchoconstriction in asthma.
abstract: We have investigated whether the inspiratory flow at which sodium cromoglycate (SCG) is inhaled influences the efficacy of SCG. Seven atopic asthmatic subjects (age 25 +/- 2 yrs) inhaled dry powder SCG from a Spinhaler on separate occasions at three flow rates, maximum (V1), 100 l.min-1 (V2), and 50 l.min-1 (V3), or placebo, according to a double-blind structured study. Thirty minutes after administration a bronchial provocation test was performed with adenosine 5'-monophosphate (AMP). Blood samples for measurement of plasma SCG concentration were taken and the area under the plasma concentration-time curve (AUC) calculated for each flow rate. Both inspiratory flow rate and AUC correlated significantly with the degree of protection afforded against AMP-induced bronchoconstriction (r = 0.73, p less than 0.001; r = 0.66, p less than 0.001). These findings indicate that the flow rate used to inhale powdered SCG is a major factor in determining the protective efficacy of this drug against bronchial challenge and therefore has important clinical implications.
authors.affiliation: Medicine I, Southampton General Hospital, England.
authors.forename: R
authors.initials: R
authors.lastname: Richards
authors.forename: S F
authors.initials: SF
authors.lastname: Simpson
authors.forename: A G
authors.initials: AG
authors.lastname: Renwick
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D000249:Adenosine Monophosphate; D000280:Administration, Inhalation / Q000379:methods; D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D004205:Cromolyn Sodium / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007320:Inspiratory Capacity; D008176:Lung Volume Measurements
chemical_list: D000249:Adenosine Monophosphate; D004205:Cromolyn Sodium