Therapeutic margin of budesonide in patients with mild to severe asthma.

BACKGROUND

The therapeutic margin of a drug is the difference between the optimal effective dose and the dose at which unacceptable adverse effects occur. This margin is particularly important in the case of therapies that are used long term for the control of chronic illnesses, such as inhaled corticosteroids (ICSs) in the treatment of asthma. Because data from controlled clinical studies indicate that the available ICSs have similar clinical efficacy, the safety profile is central to differentiating between them on the basis of their therapeutic margins. The main safety concern with long-term use and high doses of ICSs is systemic exposure that could result in such unwanted effects as cortisol suppression, a reduction in the final adult height of pediatric patients, and decreased bone mineral density.

OBJECTIVE

This article reviews data from clinical trials, including long-term prospective studies, to compare the therapeutic margin of budesonide with those of other second-generation ICSs and to determine whether there are variations in the therapeutic margin with different delivery devices, severities of disease, or patient age.

RESULTS

Based on the tolerability data for budesonide from short-term (6-12 wk) and long-term (1-9 y) studies in patients with mild to moderate persistent asthma, the dose-response and dose-tolerability curves for budesonide delivered by dry-powder inhaler can be plotted in parallel. The margin between these curves-the therapeutic margin-is favorable and consistent in pediatric and adult patients and at all degrees of asthma severity. Fewer tolerability data are available for other ICSS.

CONCLUSION

Whereas budesonide has clinical efficacy similar to that of other currently available ICSs, it has a good safety profile-and hence a favorable therapeutic margin-that is supported by long-term clinical data. Budesonides favorable therapeutic margin is probably a result of its pharmacokinetic and physical properties.