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.