Optimizing Venous Thromboembolism Prophylaxis in Burn Patients Using Enoxaparin Through PBPK Modeling.

Burn injuries cause physiological changes that alter enoxaparin pharmacokinetics, often leading to inadequate exposure and suboptimal venous thromboembolism (VTE) prophylaxis. Current weight-based dosing and anti-Xa monitoring provide limited guidance for dose optimization across burn severities. This study develops a physiologically based pharmacokinetic (PBPK) model of enoxaparin across burn phases to evaluate target attainment under standard dosing while accounting for burn severity, augmented renal clearance (ARC), and body weight, and to propose individualized dosing strategies to improve VTE prophylaxis. Real-world data of 1288 anti-Xa concentrations were collected from 408 burn patients receiving subcutaneous enoxaparin. A PBPK model was developed in healthy adults and extrapolated to burn patients by incorporating burn-specific changes, including reduced absorption and decreased antithrombin levels. This validated PBPK model for burn patients was used to simulate dosing regimens across burn severities and ARC, with model performance assessed using average fold error (AFE) and absolute average fold error (AAFE). Sub-therapeutic drug exposure was most prominent from 0 to 96 h post burn across all severities. In obese patients, dose escalation from 40 to 60 mg reduced subtherapeutic exposure from 27.3% to 16.9%. Although trough anti-Xa concentrations increased with higher doses, levels remained lower in patients with ARC compared to those with normal renal clearance (NRC), indicating the need for dose adjustment in ARC. Standard enoxaparin dosing is frequently inadequate in burn patients, particularly early after injury and in those with ARC. PBPK-informed precision dosing can improve VTE prophylaxis beyond weight-based dosing with anti-Xa monitoring alone.