Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1988 Aug;43(8):611–616. doi: 10.1136/thx.43.8.611

Effect of methacholine induced bronchoconstriction on the pulmonary distribution and plasma pharmacokinetics of inhaled sodium cromoglycate in subjects with normal and hyperreactive airways.

R Richards 1, A Haas 1, S Simpson 1, A Britten 1, A Renwick 1, S Holgate 1
PMCID: PMC461396  PMID: 3140407

Abstract

Inhalation treatment may be less effective in the presence of bronchoconstriction because of the reduced penetration of drugs into the airways. The effect of bronchoconstriction on the lung deposition and plasma pharmacokinetics of inhaled sodium cromoglycate was examined. Ten subjects attended the laboratory on three occasions. On the first occasion a bronchial provocation test was performed to determine the concentration of methacholine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20). On the two subsequent occasions subjects inhaled either saline or their PC20 methacholine, followed five minutes later by an aerosol containing sodium cromoglycate and stannous phytate labelled with technetium-99m. Twenty minutes later a gamma emission lung scan was performed to determine the intrathoracic deposition of the nebulised aerosol. The central:peripheral (C:P) ratio of lung deposition was then calculated. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for four hours. Methacholine led to a 23.4% (SEM 0.6%) lower FEV1 and a 2.8 times higher C:P ratio than those observed after saline. There was a direct correlation between log PC20 methacholine and the increase in the C:P ratio (r = 0.81). Despite these changes with methacholine, the plasma pharmacokinetics of inhaled sodium cromoglycate were not significantly different after methacholine and after saline, except that the maximum concentration achieved (Cmax) was increased. These observations suggest that the area of cromoglycate deposition and the anatomical site are less important in determining the plasma pharmacokinetics of cromoglycate than is the total dose delivered to the lung.

Full text

PDF
611

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes P. J., Nadel J. A., Roberts J. M., Basbaum C. B. Muscarinic receptors in lung and trachea: autoradiographic localization using [3H]quinuclidinyl benzilate. Eur J Pharmacol. 1982 Dec 17;86(1):103–106. doi: 10.1016/0014-2999(82)90405-8. [DOI] [PubMed] [Google Scholar]
  2. Brown K., Gardner J. J., Lockley W. J., Preston J. R., Wilkinson D. J. Radioimmunoassay of sodium cromoglycate in human plasma. Ann Clin Biochem. 1983 Jan;20(Pt 1):31–36. doi: 10.1177/000456328302000105. [DOI] [PubMed] [Google Scholar]
  3. Chai H., Farr R. S., Froehlich L. A., Mathison D. A., McLean J. A., Rosenthal R. R., Sheffer A. L., Spector S. L., Townley R. G. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975 Oct;56(4):323–327. doi: 10.1016/0091-6749(75)90107-4. [DOI] [PubMed] [Google Scholar]
  4. Dolovich M. B., Sanchis J., Rossman C., Newhouse M. T. Aerosol penetrance: a sensitive index of peripheral airways obstruction. J Appl Physiol. 1976 Mar;40(3):468–471. doi: 10.1152/jappl.1976.40.3.468. [DOI] [PubMed] [Google Scholar]
  5. Fuller R. W., Collier J. G. The pharmacokinetic assessment of sodium cromoglycate. J Pharm Pharmacol. 1983 May;35(5):289–292. doi: 10.1111/j.2042-7158.1983.tb02936.x. [DOI] [PubMed] [Google Scholar]
  6. Goldberg I. S., Lourenço R. V. Deposition of aerosols in pulmonary disease. Arch Intern Med. 1973 Jan;131(1):88–91. [PubMed] [Google Scholar]
  7. Hardy C. C., Bradding P., Robinson C., Holgate S. T. The combined effects of two pairs of mediators, adenosine with methacholine and prostaglandin D2 with histamine, on airway calibre in asthma. Clin Sci (Lond) 1986 Oct;71(4):385–392. doi: 10.1042/cs0710385. [DOI] [PubMed] [Google Scholar]
  8. Howell J. B., Altounyan R. E. A double-blind trial of disodium cromoglycate in the treatment of allergic bronchial asthma. Lancet. 1967 Sep 9;2(7515):539–542. doi: 10.1016/s0140-6736(67)90499-0. [DOI] [PubMed] [Google Scholar]
  9. Patel K. R., Tullett W. M., Neale M. G., Wall R. T., Tan K. M. Plasma concentrations of sodium cromoglycate given by nebulisation and metered dose inhalers in patients with exercise-induced asthma: relationship to protective effect. Br J Clin Pharmacol. 1986 Feb;21(2):231–233. doi: 10.1111/j.1365-2125.1986.tb05181.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pavia D., Thomson M. L., Clarke S. W., Shannon H. S. Effect of lung function and mode of inhalation on penetration of aerosol into the human lung. Thorax. 1977 Apr;32(2):194–197. doi: 10.1136/thx.32.2.194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Richards R., Dickson C. R., Renwick A. G., Lewis R. A., Holgate S. T. Absorption and disposition kinetics of cromolyn sodium and the influence of inhalation technique. J Pharmacol Exp Ther. 1987 Jun;241(3):1028–1032. [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES