Absorption and disposition kinetics of cromolyn sodium and the influence of inhalation technique

R Richards, CR Dickson, AG Renwick, RA Lewis and ST Holgate

Plasma concentrations of cromolyn sodium (SCG) have been measured in 13 normal subjects on three occasions after inhalation from a Spinhaler (20 mg) delivery system under conditions of controlled inspiratory flow rate. High inspiratory flow rates were associated with high peak plasma concentrations and areas under the plasma concentration-time curve. A 10-sec breath hold at the end of inspiration did not alter significantly the plasma concentration-time curve. Instillation of SCG (1 mg) directly into a second-order bronchus of 14 patients undergoing diagnostic examination gave plasma concentration-time curves similar to those seen in normal volunteers at high inspiratory flow rates. Additional studies in normal volunteers showed that SCG was poorly absorbed from the gastrointestinal tract. The shorter terminal half- life seen after i.v. infusion compared with inhalation indicates that the drug shows absorption rate limited disposition kinetics after inhalation. These studies in large numbers of subjects support the conclusions of limited earlier investigations that SCG is absorbed slowly but almost completely from the airways, that there is little gastrointestinal absorption of SCG, that only a small proportion of the Spinhaler dose (about 10%) reaches the airways and that the amount reaching the airways is related directly to inspiratory flow rate.

Volume 241, Issue 3, pp. 1028-1032, 06/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics