Dose-response comparison of systemic bioactivity with inhaled budesonide and triamcinolone acetonide in asthmatic adults.
BACKGROUND
Budesonide (BUD) has recently been licensed for treatment of asthma in the United States, whereas triamcinolone acetonide (TAA) has been used for many years.


OBJECTIVE
We sought to evaluate the dose-response effect of inhaled BUD and TAA in terms of adrenal, bone, and blood markers.


METHODS
Twelve asthmatic subjects (mean age, 32 years; mean FEV1, 91% of predicted value) were studied in a randomized design comparing 3 days of treatment with placebo and low (200 micrograms twice daily), medium (400 micrograms twice daily), and high (800 micrograms twice daily) doses of BUD (Pulmicort Turbuhaler, 100 micrograms) and TAA (Azmacort integrated actuator/spacer, 100 micrograms) with a 7-day period at crossover, when patients received their usual inhaled corticosteroid therapy. Measurements were made at 8 am for serum cortisol, osteocalcin, and blood eosinophils. Measurements were also made for overnight urinary cortisol/creatinine excretion.


RESULTS
For all measurements there were no significant differences between the 2 treatments at any dose level. Ratios between BUD and TAA (95% CI) at the highest dose levels were as follows: 8 am serum cortisol, 1.08-fold (0.63 to 1. 85); urinary cortisol, 1.09-fold (0.63 to 1.86); eosinophils, 0. 98-fold (0.69 to 1.38); and osteocalcin 1.05-fold (0.78 to 1.41). There was no evidence of a significant overall dose-response effect for any parameter of hypothalamo-pituitary-adrenocortical axis activity, with neither drug being significantly different from placebo at any dose. For the 3 dose levels of both drugs, total abnormal low values for 8 am serum cortisol (ie, <5.4 micrograms/dL [<150 nmol/L]) showed 2 of 36 for BUD and 2 of 36 for TAA. There was also no significant overall dose-response effect for eosinophils or osteocalcin, although both drugs were significantly (P <.05) different from placebo at the highest dose: eosinophils (x10(9)/L), placebo: 0.36, TAA: 0.24, and BUD: 0.23; and osteocalcin (nmol/L), placebo: 1.04, TAA: 0.73, and BUD: 0.77.


CONCLUSIONS
There were no significant differences in the systemic bioactivity profiles, in terms of adrenal, blood, and bone markers, between BUD administered by means of Turbuhaler and TAA administered by means of an integrated actuator/spacer in a dose range of 400 micrograms to 1600 micrograms/day. Both drugs exhibited a significant degree of detectable systemic bioactivity but only at the highest dose of 1600 micrograms/day for effects on eosinophil count and osteocalcin.
Wilson
A M
AM
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK.
Brewster
H J
HJ
Lipworth
B J
BJ
D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001682:Biological Availability; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000737:chemistry; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D010919:Placebos; D016037:Single-Blind Method; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D010919:Placebos; D015675:Osteocalcin; D019819:Budesonide; D014222:Triamcinolone Acetonide