Systemic Bioavailability and Potency of High-Dose Inhaled Corticosteroids: Results

Statistical Analysis
For each treatment, we report the percentage change from the mean of two placebo measurements with 95% confidence intervals using software (Prism 2 Software; Graph Pad Software; San Diego, CA). Wilcoxon matched pairs signed rank test was used. The percent fall in plasma cortisol level for the least suppressive treatment (budesonide via MDI spacer) was also compared with all other treatments using Wilcoxon matched pairs signed rank test.
Results
Effects of 4 mg of Budesonide Administered by Different Methods
The greatest average percentage suppression of cortisol levels was seen with the MDI alone, producing a 73% fall (vs placebo, p = 0.0002), and with the Turbohaler, which produced a 72% fall (vs placebo, p = 0.0005) (Fig 1 and Table 1). The addition of a 750-mL volume spacer to the MDI reduced plasma cortisol suppression to 42% (vs placebo, p = 0.0001), Oral budesonide produced a modest 14% fall in 9 am cortisol level (vs placebo, p = 0.04). Nebulized budesonide caused no suppression of cortisol but a nonsignificant rise of 8%. (The assay system was checked for cross-reactivity with budesonide nebulizer solution at several concentrations but no such cross-reactivity was found.) online antibiotics

Effects of Budesonide, Fluticasone, and Beclomethasone Dipropionate on 9:00 am Cortisol Suppression
Of the three drugs compared, fluticasone given by MDI and spacer produced the greatest average percentage suppression, 4 mg producing an 86% fall (vs placebo, p = 0.0005) and 2 mg producing a 72% fall (vs placebo, p = 0.0005) (Fig 2 and Table 2). The least suppressive drug was budesonide. Four milligrams of budesonide produced a 43% fall (vs placebo, p = 0.0001) and 2 mg produced a 25% fall (vs placebo, p = 0.03). Beclomethasone fell between the two in potency producing a 66% fall after a 4-mg dose (vs placebo, p = 0.0008).

Figure 1. 9:00 am cortisol levels following the administration of 4 mg of budensonide by five different devices and two placebo devices. P1, P2 = placebos; NEB = nebulizer; NH = nebuhaler; TH = Turbohaler.

Figure 1. 9:00 am cortisol levels following the administration of 4 mg of budensonide by five different devices and two placebo devices. P1, P2 = placebos; NEB = nebulizer; NH = nebuhaler; TH = Turbohaler.

Figure 2. 9:00 am serum cortisol levels with 4 mg and 2 mg of budesonide (BUD) and fluticasone (FLU) and two placebo devices. BDP = beclomethasone; P1, P2 = placebos.

Figure 2. 9:00 am serum cortisol levels with 4 mg and 2 mg of budesonide (BUD) and fluticasone (FLU) and two placebo devices. BDP = beclomethasone; P1, P2 = placebos.

Table 1—Effects of 4 mg of Budesonide Administered by Five Different Methods

Device Mean Cortisol(SD) % Change 95% CI p Value vs Placebot p Value vs Bud 4 mg via Spacert
Placebo 1 647(379)
Placebo 2 656 (387)
Bud, 4 mg nebulized 687 (463) +8 -13, +28 0.45 0.003
Bud, 4 mg oral 558 (393) -14 -34, +6 0.18 0.04
Bud, 4 mg MDI + spacer 328 (271) -42 -22, -64 0.0001
Bud, 4 mg Turbohaler 204 (290) -72 -58, -86 0.0005 0.03
Bud, 4 mg MDI (no spacer) 187 (244) -73 095 0.0002 0.02

Table 2—Effects of Budesonide, Beclomethasone, and Fluticasone Given by Large Volume Spacer

Device Mean Cortisol (SD) % Change 95% CI p Value vs Placebot p Value vs Bud 4 mg via Spacert
Placebo, mean 652 (375)
Bud, 2 mg 424 (275) 25 – 3, – 47 0.03 0.32
Bud, 4 mg 328 (271) 43 – 22, – 64 0.0001
BDP, 4 mg 215 (175) 66 – 49, – 82 0.0008 0.049
FP, 2 mg 189 (268) 72 58,5 0.0005 0.013
FP, 4 mg 93(118) 86 – 82, – 91 0.0005 0.002

Category: Inhaled Corticosteroids

Tags: adrenal suppression, beclomethasone dipropionate, bioavailability, budesonide, fluticasone propionate, inhaled corticosteroids