Brannan M D, Herron J M, Affrime M B
Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Clin Ther. 1997 Nov-Dec;19(6):1330-9. doi: 10.1016/s0149-2918(97)80008-2.
Sensitive and reproducible assessments of hypothalamic-pituitary-adrenal (HPA) axis function were used to assess the systemic exposure and tolerability of mometasone furoate aqueous nasal spray (MFNS) in 96 children aged 3 to 12 years with allergic rhinitis. In the first phase of the study, older children (aged 6 to 12 years) received MFNS at 50, 100, or 200 micrograms or placebo once daily for 7 days, and plasma cortisol concentrations were measured by radioimmunoassay before and after treatment. Plasma cortisol concentrations were not statistically significantly different from baseline values on day 7 or day 8 (1 day after treatment was stopped). Also, the mean plasma cortisol and 24-hour urinary free-cortisol concentrations of the MFNS-treated and placebo groups were not statistically significantly different. Additionally, mometasone furoate was undetectable in almost all plasma samples collected at 0.5, 1, and 2 hours after dosing on days 1 and 7. Because these findings indicated that MFNS could be safely administered to patients aged 6 to 12 years, a more rigorous assessment was conducted in younger patients (aged 3 to 5 years). The younger patients also received MFNS at 50, 100, or 200 micrograms or placebo once daily, but for a longer duration (14 days). HPA axis function was determined by the response to cosyntropin stimulation on the final day of treatment. The younger patients demonstrated a normal cortisol response to cosyntropin stimulation on day 14; that is, all the patients had an increase in plasma cortisol concentration of at least 7 micrograms/dL to at least 18 micrograms/dL. Mean plasma cortisol concentrations for the MFNS-treated groups were not statistically significantly different from the mean concentration for the placebo group, either before or after cosyntropin stimulation. MFNS was also found to be well tolerated by both the younger and older children, with headache the most frequently reported adverse event in both the placebo- and MFNS-treated groups. No clinically relevant changes in the results of physical examinations, clinical laboratory determinations, or electrocardiography were noted. These results indicate that the intranasal administration of up to 200 micrograms of MFNS once daily for up to 14 days in children aged 3 to 12 years who have allergic rhinitis is well tolerated and does not result in clinically relevant systemic exposure.
采用敏感且可重复的下丘脑 - 垂体 - 肾上腺（HPA）轴功能评估方法，对96名3至12岁患有过敏性鼻炎的儿童使用糠酸莫米松水鼻喷雾剂（MFNS）进行全身暴露和耐受性评估。在研究的第一阶段，年龄较大的儿童（6至12岁）每天一次接受50、100或200微克的MFNS或安慰剂，持续7天，并在治疗前后通过放射免疫测定法测量血浆皮质醇浓度。在第7天或第8天（停止治疗后1天），血浆皮质醇浓度与基线值无统计学显著差异。此外，MFNS治疗组和安慰剂组的平均血浆皮质醇和24小时尿游离皮质醇浓度也无统计学显著差异。另外，在第1天和第7天给药后0.5、1和2小时采集的几乎所有血浆样本中均未检测到糠酸莫米松。由于这些结果表明MFNS可安全用于6至12岁的患者，因此对年龄较小的患者（3至5岁）进行了更严格的评估。年龄较小的患者也每天一次接受50、100或200微克的MFNS或安慰剂，但持续时间更长（14天）。在治疗的最后一天，通过对促肾上腺皮质激素刺激的反应来确定HPA轴功能。年龄较小的患者在第14天对促肾上腺皮质激素刺激表现出正常的皮质醇反应；也就是说，所有患者的血浆皮质醇浓度至少增加7微克/分升至至少18微克/分升。在促肾上腺皮质激素刺激前后，MFNS治疗组的平均血浆皮质醇浓度与安慰剂组的平均浓度均无统计学显著差异。还发现年龄较小和较大的儿童对MFNS的耐受性均良好，头痛是安慰剂组和MFNS治疗组中最常报告的不良事件。体格检查、临床实验室检查或心电图结果均未发现临床相关变化。这些结果表明，在患有过敏性鼻炎的3至12岁儿童中，每天一次鼻内给予高达200微克的MFNS，持续长达14天，耐受性良好，且不会导致临床相关的全身暴露。
