S. Walker, A. J. Richards, J. Paterson
Nov 1, 1971
Citations
0
Influential Citations
15
Citations
Quality indicators
Journal
The Biochemical journal
Abstract
Disodium cromoglycate, the disodium salt of 1,3 -bis -(2 -carboxychromon -5 -yloxy) -2 -hydroxypropane, is used in the treatment of bronchial asthma (Howell & Altounyan, 1967; Kennedy, 1967). After the oral administration of disodium [3H]cromoglycate to monkeys, rabbits and rats, 1%, 2% and 4% of the dose was absorbed respectively (G. F. Moss, personal communication). However, intratracheal administration in these three species indicated that disodium cromoglycate was quickly absorbed from the lung (Moss, Jones, Ritchie & Cox, 1970). Intravenous studies (G. F. Moss, personal communication) have shown that this compound is rapidly excreted via the bile and urine in several animal species. Chromatography of bile and urine indicated that all the recovered radioactivity was in unchanged disodium cromoglycate. The fate of inhaled disodium [14C]cromoglycate has been examined in asthmatic patients. Maximumplasma concentrations (9ng/ml) were obtained within l5min ofinhaling the disodium cromoglycate (20mg, 33,uCi), and the half-life in plasma was 81 min. The urinary-excretion findings suggest that drug reaching the lung is rapidly absorbed and excreted. Only 2% ofthe inhaled dose appeared in the 24h urine, 84% being recovered in the faeces. The fate of orally administered disodium [14C]cromoglycate (20mg, 8,uCi) was examined. The drug was poorly absorbed from the gastrointestinal tract, only 0.4% of the dose appearing in the 24h urine and 82% being recovered from the faeces. No metabolites were detected chromatographically, The intravenous administration of disodium [14C]cromoglycate (4mg, 6,uCi) resulted in approximately equal amounts being excreted in the urine and the faeces. Disodium cromoglycate is highly polar with a molecular weight of 512, and thus satisfies the criteria for biliary excretion (Millburn, Smith & Williams, 1967). A comparison of our results with the animal data shows that the monkey handles the drug in a similar manner to man.