Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol @entity134 , XXXX .

@entity748 @entity1 @entity2715 @entity565 @entity228 @entity134 @entity4184 @entity701 @entity230
The influence of various dosing regimens on the response of @entity748 @entity1 to aerosol @entity134 was investigated. @entity4184 , a topically active @entity228 like @entity2715 , 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 @entity1 (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 @entity701 levels increased approximately linearly on log dose @entity4184 (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 @entity565 was in remission but became so with @entity565 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 @entity1 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 @entity1 can increase the antiasthmatic efficacy of this aerosol @entity134 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 @entity230 currently used to treat @entity565 .
