Model-Informed Drug Development Supports Full Approval of Ibuprofen Injection in Chinese Pediatric Patients With...

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.