Skoner David E
Department of Pediatrics, Division of Allergy, Asthma and Immunology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA.
Clin Ther. 2003;25 Suppl C:C61-74. doi: 10.1016/s0149-2918(03)80306-5.
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.
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.
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.
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.
药物的治疗窗是最佳有效剂量与出现不可接受的不良反应的剂量之间的差值。对于长期用于控制慢性病的疗法，如吸入性糖皮质激素（ICSs）治疗哮喘，这一治疗窗尤为重要。由于对照临床研究的数据表明现有的ICSs具有相似的临床疗效，因此安全性在基于治疗窗区分它们时至关重要。长期使用高剂量ICSs的主要安全问题是全身暴露，这可能导致诸如皮质醇抑制、儿科患者最终成年身高降低以及骨密度下降等不良影响。
本文回顾临床试验数据，包括长期前瞻性研究，以比较布地奈德与其他第二代ICSs的治疗窗，并确定治疗窗是否因不同的给药装置、疾病严重程度或患者年龄而有所不同。
基于布地奈德在轻度至中度持续性哮喘患者短期（6 - 12周）和长期（1 - 9年）研究中的耐受性数据，可绘制干粉吸入器递送的布地奈德的剂量 - 反应和剂量 - 耐受性曲线。这些曲线之间的差值——治疗窗——在儿科和成年患者以及所有哮喘严重程度下都是良好且一致的。其他ICSs的耐受性数据较少。
虽然布地奈德具有与其他现有ICSs相似的临床疗效，但它具有良好的安全性——因此具有良好的治疗窗——这得到了长期临床数据的支持。布地奈德良好的治疗窗可能是其药代动力学和物理性质的结果。
