Systemic Bioavailability and Potency of High-Dose Inhaled Corticosteroids: Materials and Methods
Sixteen healthy, nonsmoking volunteers aged 25 to 42 years completed the study (12 were men). All were steroid naive and taking no other medication. Each subject gave written informed consent, and the study was approved by the Salford Local Research Ethics Committee.
This was a double-blind, crossover, placebo-controlled trial. For the first experiment, subjects took 4 mg of budesonide through four inhaler systems and orally (to assess the effects of GI absorption) Reading here zyrtec tablets. Each subject received, in random order, seven double-blind treatments of which two (randomly chosen) were placebo: (1) MDI without spacer device (20 inhalations from Pulmicort 200-^g inhaler; Astra Pharmaceuticals; Kings Langley, UK); (2) MDI and 750-mL spacer (20 inhalations of Pulmicort 200-^g inhaler using Nebuhaler 750-mL spacer; Astra Pharmaceuticals); (3) dry powder inhaler (10 inhalations of Pulmicort 400-^g Turbohaler; Astra Pharmaceuticals); (4) nebulized budesonide (four Pulmicort Respules, each containing 1 mg budesonide in 2 mL; Astra Pharmaceuticals); the solution was nebulized using a jet stream nebulizer (System 22; Medic-Aid; West Sussex, UK); (5) budesonide was taken orally (subjects swallowed the contents of four Pulmicort Respules); (6) placebo MDI inhaler, 20 actuations; and (7) placebo MDI inhaler, 10 actuations.
All drugs were taken at 11:00 pm, and 9:00 am plasma cortisol levels were measured the following day.
In the second experiment, the effects of the three commonly prescribed inhaled corticosteroids were compared. Each subject took the following in random order: (1) 4 mg of fluticasone (16 inhalations of Flixotide 250-^g inhaler; Allen and Hanbury’s; Stockley Park, UK) by MDI and spacer; (2) 4 mg of beclometha-sone dipropionate (16 inhalations of Becloforte 250-^g inhaler; Allen and Hanbury’s) by MDI and spacer; (3) 2 mg of fluticasone (8 inhalations of Flixotide 250-^g inhaler; Allen and Hanbury’s) by MDI and spacer; and (4) 2 mg of budesonide (10 inhalations of Pulmicort 200-^g inhaler using Nebuhaler 750-mL spacer; Astra Pharmaceuticals) by MDI and spacer. The results of the inhalation of 4 mg of budesonide through MDI and spacer and the two placebo inhalations from the first experiment were utilized in the second experiment.