Abstract
In a previous study we showed, in both asthmatic patients and in healthy subjects, a marked increase in plasma concentration of nedocromil immediately following an exercise challenge with associated FEV1 measurements. To identify which component of the exercise challenge is responsible, we have now studied the effect of various manoeuvres on plasma nedocromil concentration in eight healthy subjects after inhalation of 1 ml nedocromil solution (1% w/v) via a Wright nebuliser. Each patient was dosed on six occasions, separated by at least 3 days. Between 15 and 23 min after dosing one of the following manoeuvres was performed: control (no manoeuvre); steady exercise for 8 min, a series of FEV1 measurements, exercise plus FEV1 measurements, three Valsalva manoeuvres and hyperventilation for 3 min. Mean plasma drug concentrations under control conditions were similar at 15 and 23 min after dosing. However, there were significant increases in plasma drug concentration following exercise, FEV1 manoeuvres and exercise plus FEV1 manoeuvre. There were no significant changes in plasma drug concentration following Valsalva manoeuvres and hyperventilation. The results suggest that certain manoeuvres increase the absorption of nedocromil sodium, probably as a consequence of an increase in lung volume.
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Selected References
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- Cross C. E., Gong H., Jr, Kurpershoek C. J., Gillespie J. R., Hyde R. W. Alterations in distribution of blood flow to the lung's diffusion surfaces during exercise. J Clin Invest. 1973 Feb;52(2):414–421. doi: 10.1172/JCI107198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Egan E. A. Response of alveolar epithelial solute permeability to changes in lung inflation. J Appl Physiol Respir Environ Exerc Physiol. 1980 Dec;49(6):1032–1036. doi: 10.1152/jappl.1980.49.6.1032. [DOI] [PubMed] [Google Scholar]
- Gardner J. J., Preston J. R., Gilbert C. M., Wilkinson D. J., Lockley W. J., Brown K. A radioimmunoassay method for the determination of nedocromil sodium in plasma and urine. J Pharm Biomed Anal. 1988;6(3):285–297. doi: 10.1016/0731-7085(88)80055-4. [DOI] [PubMed] [Google Scholar]
- Neale M. G., Brown K., Foulds R. A., Lal S., Morris D. A., Thomas D. The pharmacokinetics of nedocromil sodium, a new drug for the treatment of reversible obstructive airways disease, in human volunteers and patients with reversible obstructive airways disease. Br J Clin Pharmacol. 1987 Oct;24(4):493–501. doi: 10.1111/j.1365-2125.1987.tb03203.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neale M. G., Brown K., Hodder R. W., Auty R. M. The pharmacokinetics of sodium cromoglycate in man after intravenous and inhalation administration. Br J Clin Pharmacol. 1986 Oct;22(4):373–382. doi: 10.1111/j.1365-2125.1986.tb02905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel K. R., Kerr J. W. The dose-duration effect of sodium cromoglycate in exercise-induced asthma. Clin Allergy. 1984 Jan;14(1):87–91. doi: 10.1111/j.1365-2222.1984.tb02195.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Patel K. R., Wall R. T. Dose-duration effect of sodium cromoglycate aerosol in exercise-induced asthma. Eur J Respir Dis. 1986 Oct;69(4):256–260. [PubMed] [Google Scholar]
- Rizk N. W., Luce J. M., Hoeffel J. M., Price D. C., Murray J. F. Site of deposition and factors affecting clearance of aerosolized solute from canine lungs. J Appl Physiol Respir Environ Exerc Physiol. 1984 Mar;56(3):723–729. doi: 10.1152/jappl.1984.56.3.723. [DOI] [PubMed] [Google Scholar]
- WEST J. B., DOLLERY C. T. Distribution of blood flow and ventilation-perfusion ratio in the lung, measured with radioactive carbon dioxide. J Appl Physiol. 1960 May;15:405–410. doi: 10.1152/jappl.1960.15.3.405. [DOI] [PubMed] [Google Scholar]
- WEST J. B. Regional differences in gas exchange in the lung of erect man. J Appl Physiol. 1962 Nov;17:893–898. doi: 10.1152/jappl.1962.17.6.893. [DOI] [PubMed] [Google Scholar]
