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: Ne sought to evaluate the dos e-response effect of inhaled BUD and TAA in terms of adrenal, bone, an d blood markers, Methods: Twelve asthmatic subjects (mean age, 32 Sear s; mean FEV1, 91% of predicted value) were studied in a randomized des ign comparing 3 days of treatment with placebo and low (200 mu g twice daily), medium (400 mu g twice daily), and high (800 mu g twice daily ) doses of BUD (Pulmicort Turbuhaler, 100 mu g) and TAA (Azmacort inte grated actuator/spacer, 100 mu g) with a 7-day period at crossover, wh en patients received their usual inhaled corticosteroid therapy. Measu rements were made at 8 AM for serum cortisol, osteocalcin, and blood e osinophils. Measurements were also made for overnight urinary cortisol /creatinine excretion. Results: For all measurements there were no sig nificant differences between the 2 treatments at any dose level. Ratio s between BUD and TAA (95% CI) at the highest dose levels were as foll ows: 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 o steocalcin 1.05-fold (0.78 to 1.41), There was no evidence of a signif icant overall dose-response effect for any parameter of hypothalamo-pi tuitary-adrenocortical axis activity, with neither drug being signific antly different from placebo at any dose. For the 3 dose levels of bot h drugs, total abnormal low values for 8 AM serum cortisol (ie, <5.4 m u g/dL [<150 nmol/L]) showed 2 of 36 for BUD and 2 of 36 for TAA, Ther e was also no significant overall dose-response effect for eosinophils or osteocalcin, although both drugs were significantly (P < .05) diff erent from placebo at the highest dose: eosinophils (x 10(9) g/L), pla cebo: 0.36, TAA: 0.24, and BUD: 0.23; and osteocalcin (nmol/L), placeb o: 1.04, TAA: 0.73, and BUD: 0.77. Conclusion: There were no significa nt differences in the systemic bioactivity profiles, in terms of adren al, blood, and bone markers, between BUD administered by means of Turb uhaler and TAA administered by means of an integrated actuator/spacer in a dose range of 400 mu g to 1600 mu g/day. Both drugs exhibited a s ignificant degree of detectable systemic bioactivity but only at the h ighest dose of 1600 mu g/day for effects on eosinophil count and osteo calcin.