de la Motte Stephan, Beier Jutta, Schmid Karin, Pascual Silvia, Jansat Josep Maria, Gil Esther Garcia
Harrison Clinical Research Deutschland GmbH, Munich, Germany.
Int J Clin Pharmacol Ther. 2012 Jun;50(6):403-12. doi: 10.5414/CP201628.
To investigate the pharmacokinetics, safety and tolerability of aclidinium bromide 200 μg and 400 μg after a single dose and repeated once-daily doses in younger and elderly patients with moderate or severe chronic obstructive pulmonary disease (COPD).
Younger (40-59 years; n = 12) and elderly (≥ 70 years; n = 12) patients were treated with aclidinium via the Genuair® inhaler. Patients received once-daily aclidinium 200 μg for 3 days; after a 7-day washout period, patients received once-daily aclidinium 400 μg for 3 days. Pharmacokinetic analyses were conducted on plasma and urine on Days 1 and 3 of both treatment periods. Safety and tolerability were assessed.
Aclidinium showed similar linear and time-independent pharmacokinetics in younger and elderly patients at each dose level and day of treatment. For both age groups at each dose level and day, aclidinium appeared rapidly in the plasma with a median tmax between 10 and 15 min; concentrations of aclidinium in the plasma declined rapidly with a t1/2 between 1 and 3 h. Plasma exposure with the 400 μg dose was ~ 2-fold higher than for the 200 μg dose in both age groups on both days. For both age groups, urinary excretion of aclidinium over 24 h was < 0.15% of the dose at each dose and day. Aclidinium 200 μg and 400 μg were safe and well tolerated in both age groups.
These data suggest that no dose adjustment of aclidinium is required when treating elderly patients with COPD.
研究200μg和400μg阿地溴铵在中度或重度慢性阻塞性肺疾病（COPD）的年轻和老年患者中单次给药及每日重复给药后的药代动力学、安全性和耐受性。
年轻（40 - 59岁；n = 12）和老年（≥70岁；n = 12）患者通过Genuair®吸入器使用阿地溴铵进行治疗。患者每日一次给予200μg阿地溴铵，持续3天；经过7天的洗脱期后，患者每日一次给予400μg阿地溴铵，持续3天。在两个治疗周期的第1天和第3天对血浆和尿液进行药代动力学分析。评估安全性和耐受性。
在每个剂量水平和治疗日，阿地溴铵在年轻和老年患者中显示出相似的线性和非时间依赖性药代动力学。在每个剂量水平和治疗日的两个年龄组中，阿地溴铵在血浆中迅速出现，中位达峰时间在10至15分钟之间；血浆中阿地溴铵浓度迅速下降，半衰期在1至3小时之间。在两个年龄组的两天中，400μg剂量的血浆暴露量比200μg剂量高约2倍。对于两个年龄组，在每个剂量和治疗日，24小时内阿地溴铵的尿排泄量均<剂量的0.15%。200μg和400μg阿地溴铵在两个年龄组中均安全且耐受性良好。
这些数据表明，在治疗老年COPD患者时无需调整阿地溴铵的剂量。
