在老年健康受试者中比较新型选择性环氧化酶-2 抑制剂伊美昔布的药代动力学和安全性。
Comparative Pharmacokinetics and Safety of Imrecoxib, a Novel Selective Cyclooxygenase-2 Inhibitor, in Elderly Healthy Subjects.
机构信息
Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, Chengdu, People's Republic of China.
出版信息
Drug Des Devel Ther. 2022 Nov 8;16:3865-3876. doi: 10.2147/DDDT.S387508. eCollection 2022.
BACKGROUND
Imrecoxib is a novel and moderately selective cyclooxygenase-2 inhibitor with properties of anti-inflammation and alleviating pain, which is widely applied in osteoarthritis patients. The pharmacokinetic data supporting imrecoxib's rational use in elderly population are not available.
PURPOSE
The study aims to investigate the pharmacokinetics of imrecoxib and its main metabolites and explore the safety of imrecoxib in elderly healthy subjects.
METHODS
A total of 19 healthy subjects including 10 non-elderly and 9 elderly subjects received single dose of 100 mg imrecoxib under fasting condition. Pharmacokinetics, safety and tolerability profiles were assessed.
RESULTS
After oral administration of single dose of 100 mg imrecoxib, it was absorbed into plasma with median time to reach peak concentration (T) around 2 hours. The concentration-time curves of imrecoxib (M0) showed higher interindividual variability in elderly subjects compared with non-elderly subjects. Peak concentration (C) of M0, its hydroxyl metabolite M1 and carboxylated metabolite M2 in plasma increased by 39%, 21% and 17%, and area under concentration-time curve from time 0 to time t (AUC) of M0, M1 and M2 in plasma increased by 34%, 13% and 27%, respectively, in elderly subjects compared with non-elderly subjects. The 90% CIs of geometric mean ratios of C, AUC and AUC of M0, M1 and M2 between the two groups were not located within 80-125%, indicating C, AUC and AUC were not completely equivalent between non-elderly and elderly healthy subjects. However, comparison of pharmacokinetic data of M0, M1 and M2 between the two groups showed no significant difference (>0.05). Imrecoxib was well tolerated in both non-elderly and elderly healthy subjects, especially with favorable gastrointestinal and cardiovascular safety profiles.
CONCLUSION
Pharmacokinetic and safety profiles of imrecoxib in elderly healthy subjects indicated that no dose adjustment should be required for elderly population.
背景
Imrecoxib 是一种新型、中度选择性环氧化酶-2 抑制剂，具有抗炎和缓解疼痛的作用，广泛应用于骨关节炎患者。目前尚无支持在老年人群中合理使用 Imrecoxib 的药代动力学数据。
目的
本研究旨在探讨 Imrecoxib 及其主要代谢物的药代动力学特征，并评估其在老年健康受试者中的安全性。
方法
19 名健康受试者（包括 10 名非老年受试者和 9 名老年受试者）空腹单次口服 100mg Imrecoxib。评估药代动力学、安全性和耐受性。
结果
口服单剂量 100mg Imrecoxib 后，约 2 小时达到血药峰浓度（T）。老年受试者 Imrecoxib（M0）的浓度-时间曲线个体间差异高于非老年受试者。与非老年受试者相比，老年受试者 M0、其羟基代谢物 M1 和羧基代谢物 M2 的血药峰浓度（C）分别增加了 39%、21%和 17%，M0、M1 和 M2 的血药浓度-时间曲线下面积（AUC）分别增加了 34%、13%和 27%。两组间 M0、M1 和 M2 的 C、AUC 和 AUC 的几何均数比值的 90%置信区间（CI）均不在 80%~125%范围内，表明非老年和老年健康受试者间 C、AUC 和 AUC 不完全等效。然而，两组间 M0、M1 和 M2 的药代动力学数据比较无显著差异（>0.05）。Imrecoxib 在非老年和老年健康受试者中均具有良好的耐受性，尤其是胃肠道和心血管安全性良好。
结论
老年健康受试者的 Imrecoxib 药代动力学和安全性特征表明，老年人群无需调整剂量。
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