Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide.

The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated. Budesonide, a topically active corticosteroid like beclomethasone dipropionate, was given q.i.d. or b.i.d., in the morning or A.M./P.M., at doses of 400, 800, and 1600 micrograms/day. Each patient (n = 34) took every treatment combination for 2 wk. The antiasthmatic and systemic effects, measured by changes in peak expiratory flow rate (PEFR), blood eosinophils, and serum cortisol levels increased approximately linearly on log dose budesonide (p less than 0.0005). Systemic effects of the drug were nonsignificant at low dosage. At high dosage, morning dosing conserved hypothalamic-pituitary-adrenal function, but at the cost of a marginal reduction in efficacy (delta PEFR, p = 0.12). Having the dose frequency reduced the antiasthmatic potency of the drug, i.e., PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage (p = 0.002). This effect was not evident when asthma was in remission but became so with asthma in relapse. Overall, the q.i.d. A.M./P.M. regimen showed the best risk-benefit relationships. The data indicate (1) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug's long-term efficacy are likely to lead to the reverse effect, (2) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day, and (3) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs (or apparent risk) by simply increasing dosing frequency. These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma.