Concomitant administration of low-dose prednisolone protects against in vivo beta2-adrenoceptor subsensitivity induced by regular formoterol

Chest
K S TanB J Lipworth

Abstract

To assess whether concomitant administration of low-dose prednisolone (PRED) with regular inhaled formoterol (FM) might prevent the occurrence of beta2-adrenoceptor (beta2-AR) tachyphylaxis. Eleven healthy male subjects (mean age, 29 years) were randomized to receive 1 week with either inhaled FM, 24 microg bid, and placebo tablets (PL), or inhaled FM, 24 microg bid, and oral PRED, 15 mg daily, in double-blind, crossover fashion, with a 2-week washout between treatments. A dose-response curve (DRC) for systemic beta2-responses to inhaled salbutamol (800 to 3,200 microg) was constructed before and after each treatment period (ie, FM + PL or FM + PRED). Lymphocyte beta2-AR density (Bmax) and maximal cyclic adenosine monophosphate response to isoproterenol (isoprenaline) (Emax) were evaluated ex vivo at each visit; 8 AM serum cortisol level was also evaluated as a marker of systemic glucocorticoid activity. Comparisons for DRC were made as peak responses and area under curve (AUC). There was significant (p < 0.05) subsensitivity of systemic beta2-AR responses (as AUC) following FM + PL: for heart rate (before vs after), 760 vs 340 beats (95% confidence interval [CI], 160 to 680), for tremor 0.39 vs 0.19 log units/h (95% CI, 0.01 t...Continue Reading

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Citations

Oct 6, 2001·American Journal of Respiratory and Critical Care Medicine·J C Kips, R A Pauwels
Jun 26, 2001·European Journal of Drug Metabolism and Pharmacokinetics·M G DerksC J Van Boxtel
Jan 15, 2004·American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions·Hanneke J van der Woude, René Aalbers
Oct 5, 2019·Drugs·Christian DomingoAna Sogo
Sep 19, 2002·British Journal of Clinical Pharmacology·Brian J Lipworth
Mar 9, 2004·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Catherine M Jackson, Brian Lipworth

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