医学
布洛芬
药代动力学
不利影响
临床试验
基于生理学的药代动力学模型
药物开发
人口
药品
微量剂量
加药
上市后监督
麻醉
非甾体
药效学
药理学
临床研究
Cmin公司
重症监护医学
临床药理学
群体药代动力学
非金属
中国人口
药物不良反应
梅德林
作者
Qianxi Lou,Haiyan Zhou,Zhuokang Wang,Jing Cao,Bo-hao Tang,Yi Zheng,Ying Wang,Xiaowei Bai,John van den Anker,Guo-xiang Hao,Enmei Liu,Wei Zhao
摘要
Ibuprofen is a commonly used nonsteroidal anti‐inflammatory drug, and its injectable form has specific clinical applications. However, ibuprofen injection has not been approved for use in Chinese children. This study aimed to support its approval in this population using a model‐informed drug development (MIDD) approach. Ibuprofen injection (Fenliping®) received approval for Chinese pediatric indications in 2019, with a clinical trial waiver based on pediatric extrapolation using modeling and simulation. A physiologically based pharmacokinetic (PBPK) model was used to assess ethnic differences and determine the optimal dose for Chinese children. A single‐arm, open‐label trial was conducted in 40 pediatric patients aged 0.5–6 years to confirm the appropriateness of the 10 mg/kg dose. Body temperature, pain scores, and adverse events were collected to evaluate efficacy, safety, tolerability, and were used as clinical endpoints for exposure–response analysis. Sparse sampling was applied for pharmacokinetic analysis. A population pharmacokinetic (PopPK) model was developed using clinical data and used to refine the PBPK model and compare pharmacokinetics between Chinese and Caucasian children. Exposure–response analysis evaluated the relationship between exposure and clinical outcomes. The PBPK model showed minimal ethnic impact on pharmacokinetics, supporting a 10 mg/kg dose. In febrile patients, 89.5% achieved temperature < 38.5°C within 4 hours. Pain scores decreased below threshold. One mild drug‐related adverse event occurred. PK parameters were comparable across ethnicities, and no exposure–response relationship was observed. The MIDD approach supported full approval of ibuprofen injection in Chinese children. A 10 mg/kg dose was effective, safe, and well‐tolerated.
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