Xu Jian, Sabarinath Sreedharan Nair, Derendorf Hartmut
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Eur J Pharm Sci. 2009 Jan 31;36(1):110-21. doi: 10.1016/j.ejps.2008.10.016. Epub 2008 Nov 5.
Exposure of inhaled corticosteroids (ICSs) in pediatrics results in adrenal suppression and growth inhibition. The objective of this study was to assess the relationship of ICS mediated growth retardation with cortisol suppression in asthmatic children. A meta-analysis approach was performed with 33 published articles. Growth velocity (GV) data were obtained from the literature for evaluation of growth. Cumulative cortisol suppression within 24h (CCS%) was calculated at steady state with a validated algorithm. Consolidated GV and CCS% data were employed for model development. A linear mixed effects model was developed to adequately describe the relationship between GV and CCS%. No impact of tested covariates was observed. Population estimate of the rate of change in GV was -0.06cm/year/CCS% (12.7%, coefficient of variation) for both stadiometry and knemometry methods. However, GV from stadiometry is expected to be approximately three fold higher than that from knemometry when cortisol suppression was not presented. The final model was evaluated with posterior predictive check and pattern check approaches. The results from this study elucidate CCS% as an excellent predictor of ICS mediated growth retardation in asthmatic children.
儿科患者吸入糖皮质激素（ICSs）会导致肾上腺抑制和生长抑制。本研究的目的是评估ICS介导的生长迟缓与哮喘儿童皮质醇抑制之间的关系。采用荟萃分析方法，纳入了33篇已发表的文章。从文献中获取生长速度（GV）数据以评估生长情况。使用经过验证的算法在稳态下计算24小时内的累积皮质醇抑制率（CCS%）。合并后的GV和CCS%数据用于模型开发。建立了线性混合效应模型以充分描述GV和CCS%之间的关系。未观察到所测试协变量的影响。对于身高测量法和下肢长度测量法，GV变化率的总体估计值均为-0.06厘米/年/CCS%（变异系数为12.7%）。然而，在未出现皮质醇抑制时，身高测量法得出的GV预计比下肢长度测量法高出约三倍。采用后验预测检验和模式检验方法对最终模型进行评估。本研究结果表明，CCS%是哮喘儿童中ICS介导的生长迟缓的良好预测指标。
