Optimizing ibuprofen dosing: insights from in vivo and virtual pharmacokinetic trials

Ibuprofen, a common non-steroidal anti-inflammatory drug (NSAID), is widely used in over-the-counter (OTC) settings for pain and fever management, with a maximum daily dose of 1200 mg recommended for non-prescription use. The clinical efficacy of ibuprofen is influenced by formulation-specific differences in drug release profiles. This study systematically compared four ibuprofen formulations: immediate-release (IR) 400 mg tablets, IR 200 mg tablets, lysinate salt equivalent to 400 mg ibuprofen, and a novel bi-layer tablet integrating immediate- and sustained-release (IR/SR) components. Both, in vivo pharmacokinetic (PK) data and physiologically based PK modeling were employed to evaluate absorption kinetics, plasma concentration-time profiles, and therapeutic duration. Plasma concentration thresholds of 6.8 µg/mL and 10.1 µg/mL were used to assess onset and duration of action. The IR/SR 400 mg bi-layer tablet maintained plasma concentrations above these thresholds for eight hours, extending therapeutic coverage by 2-3.5 h compared to other IR formulations. Virtual PK simulations indicated that only IR 200 mg (six doses/day) and IR/SR 400 mg (three doses/day) regimens sustained therapeutic levels over 24 h without surpassing OTC limits. The reduced dosing frequency and prolonged efficacy of the IR/SR formulation support its suitability for providing continuous pain and fever relief.