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Effects of oral and inhaled corticosteroid on lymphocyte β 2 ‐adrenoceptor function in asthmatic patients
Author(s) -
Tan Kia Soong,
McFarlane Lesley C.,
Lipworth Brian J.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.00627.x
Subject(s) - fluticasone , medicine , prednisolone , corticosteroid , placebo , fluticasone propionate , lymphocyte , endocrinology , gastroenterology , inhalation , anesthesia , alternative medicine , pathology
Aims We have previously demonstrated that a single dose of oral prednisolone but not single doses of inhaled fluticasone had facilitatory effects on lymphocyte β 2 ‐adrenoceptor (AR) function. To address possible differences in steady‐state time‐course, the aim of this study was to determine if repeated dosing with inhaled fluticasone would have facilitatory effects on lymphocyte β 2 ‐AR. Plasma cortisol was also evaluated as a measure of systemic bioactivity. Methods Ten asthmatic subjects, mean (s.e.mean) age 29 (3) years, FEV 1 89 (5) % predicted, were randomised in a double‐blind crossover study to receive inhaled placebo (PL), inhaled fluticasone 1000 μg day −1 (F1000) and inhaled fluticasone 2000 μg day −1 , each for 4 days and also a single dose of oral prednisolone 50 mg (PRED). Prednisolone was given as open medication. The last dose of study drug was taken at 22.00 h and subjects attended the laboratory at 08.00 h the following day. Results β 2 ‐AR density (B max ; fmol/10 6 cells) was significantly increased after PRED compared with PL and inhaled fluticasone. B max (geometric mean) after each treatment were: PL 1.51, F1000 1.20, F2000 1.20 and PRED 2.14 (a 1.4 fold difference PRED vs PL; 95% CI 1.05 to 1.95; P<0.001). There was significant (P<0.001) suppression of plasma cortisol (nmol l −1 ) following F2000 and PRED compared with PL: 393.8, F1000 302.1, F2000 205.0 (95% CI F2000 vs PL 58.1 to 319.4) and PRED 87.0 (95% CI PRED vs PL 176.2 to 437.5). The estimated milligram equivalence ratio for adrenal suppression was calculated at 1:11 for fluticasone vs prednisolone. Conclusions Repeated dosing with high‐dose inhaled fluticasone did not up‐regulate lymphocyte β 2 ‐AR as compared with a single dose of oral prednisolone, despite having significantly suppressed early morning plasma cortisol. This study confirms our previous finding of a dissociation in sensitivity between effects of inhaled corticosteroid on adrenal suppression and lymphocyte β 2 ‐AR regulation, at least for doses up to 2 mg day −1 of fluticasone.