Ollier Celine, Sent Ulrike, Mesquita Margarida, Michel Martin C
PKDM-TMED Department, Sanofi-Aventis, PK-Biopharm, Montpellier, France.
Sanofi-Aventis, CHC Medical Affairs, Frankfurt am Main, Germany.
Pulm Ther. 2020 Jun;6(1):119-130. doi: 10.1007/s41030-020-00116-7. Epub 2020 May 5.
Ambroxol is used in the treatment of acute and chronic respiratory conditions characterized by abnormal mucus secretion and impaired mucus transport and is available in a variety of formulations. This study aimed to compare the steady-state (SS) pharmacokinetic characteristics of extended-release (ER) 75-mg retard capsules with two immediate-release (IR) formulations (60-mg effervescent tablets and 30-mg tablets) over a 24-h period.
An open-label, randomized, three-period, six-sequence crossover study was conducted in healthy volunteers aged 18-45 years who had a normal body mass index. The test (ER 75-mg retard capsule once daily) and reference treatments (half of IR 60-mg effervescent tablet twice daily or 30-mg IR tablet twice daily) were administered on days 1-5 of each treatment period. Meals were standardized and concomitant therapy was prohibited. Blood samples for pharmacokinetic assessment were collected on day 5 (SS) of each treatment period. The co-primary endpoints were exposure (AUC) and maximum plasma level (C).
Twenty-four participants received ambroxol (male n = 13, 54.2%; mean ± standard deviation [SD] age 25.0 ± 6.4 years) and 23 completed the study. ER retard capsules provided similar AUC compared to IR tablets (geometric means ratio [GMR] 110.7%; 90% confidence interval [CI] 99.8%, 122.7%) and effervescent tablets (GMR 106.9%; 90% CI 100.3%, 114.0%). ER retard capsules provided similar C compared to IR tablets (GMR 84.7%, 90% CI 77.0%, 93.3%), and lower C compared to effervescent tablets (GMR 80.9%, 90% CI 73.9%, 88.6%). Time to C (t) was longer with ER retard capsules (6.0 h) than with IR tablets (2.0 h) or effervescent tablets (1.0 h).
ER ambroxol 75-mg retard capsules given once daily showed a similar pharmacokinetic profile to IR ambroxol formulations and therefore can be used instead of these in the treatment of respiratory conditions. CLINICALTRIALS.
NCT02036775.
氨溴索用于治疗以黏液分泌异常和黏液转运受损为特征的急慢性呼吸道疾病，有多种剂型。本研究旨在比较75毫克缓释胶囊与两种速释剂型（60毫克泡腾片和30毫克片剂）在24小时内的稳态药代动力学特征。
在18至45岁、体重指数正常的健康志愿者中进行了一项开放标签、随机、三周期、六序列交叉研究。每个治疗周期的第1至5天给予试验药物（每日一次75毫克缓释胶囊）和对照药物（每日两次60毫克泡腾片的一半或每日两次30毫克速释片）。饮食标准化，禁止合并用药。在每个治疗周期的第5天（稳态）采集血样进行药代动力学评估。共同主要终点为暴露量（AUC）和血浆最高浓度（C）。
24名参与者接受了氨溴索治疗（男性13名，占54.2%；平均年龄±标准差[SD]为25.0±6.4岁），23名完成了研究。与速释片相比，缓释胶囊的AUC相似（几何均值比[GMR]为110.7%；90%置信区间[CI]为99.8%，122.7%），与泡腾片相比也相似（GMR为106.9%；90%CI为100.3%，114.0%）。与速释片相比，缓释胶囊的C相似（GMR为84.7%，90%CI为77.0%，93.3%），与泡腾片相比C较低（GMR为80.9%，90%CI为73.9%，88.6%）。缓释胶囊达到C的时间（t）（6.0小时）比速释片（2.0小时）或泡腾片（1.0小时）长。
每日一次服用75毫克氨溴索缓释胶囊的药代动力学特征与氨溴索速释剂型相似，因此可用于替代这些剂型治疗呼吸道疾病。临床试验。
NCT02036775
