PWI-004 - IS ENOXAPARIN DOSING ADEQUATE FOR THROMBOPROPHYLAXIS IN BURN PATIENTS? INSIGHTS FROM REAL-WORLD DATA USING PHARMACOMETRIC MODELING.

B. Shenkoya¹, V. Yellepedi², M. Gopalakrishnan³, A. Prazak⁴; ¹University of Maryland Baltimore, MD, USA, ²The University of Utah, UT, USA, ³University of Maryland, Baltimore, Baltimore, MD, USA, ⁴University of Utah Hospitals and Clinics, Salt Lake, UT, USA.

Background: Enoxaparin dosing in burn patients is challenging due to physiological changes affecting drug absorption, distribution, and clearance. Over one-third of burn patients fail to reach target prophylactic anti-factor Xa (anti-Xa) levels (0.2–0.4 U/mL) with current equation-based dosing. This study aimed to develop a population pharmacokinetic (PK) model for enoxaparin in burn patients and assess target attainment using both current and model-based dosing regimens.

Methods: Real-world data from 408 burn patients who received enoxaparin for thromboembolism prophylaxis were retrieved from electronic health record of University of Utah Burn Center between 2014 and 2023. The dataset included 15,516 doses and 1,372 anti-Xa measurements. Various PK models were tested to identify the best structural model. The impacts of total burn surface area (TBSA), body weight, and other covariates on clearance (CL/F) and volume of distribution (Vc/F) were examined. The selected model was used to evaluate target attainment with current dosing and to propose an alternate dosing regimen through simulations.

Results: A one-compartment model adequately described the data, with estimated CL/F of 1.56 L/h and Vc/F of 22.1 L, consistent with values reported for critically ill patients who share similar fluid management and augmented clearance. TBSA and body weight significantly impacted CL/F and Vc/F, explaining over 25% of variability. Patients with TBSA >20% had about twice the Vc/F compared to those with TBSA < 10%. Only 56% of burn patients reached the target enoxaparin anti-Xa levels about four hours after the third dose with the current dosing. However, model-based dosing, including both flat (M1) and loading-plus-flat (M2) dosing, improved target attainment to 90% and 83%, respectively. The simulations indicate that the proposed dosing improves target attainment, especially for patients with larger TBSA or higher body weight. However, further benefit-risk evaluation is needed to assess bleeding risks in clinical practice. The proposed dosing regimen is shown in Table 1.

Conclusion: In conclusion, a population PK model of enoxaparin was successfully developed for burn patients using real-world data and used to propose an alternative dosing regimen with higher target attainment in prophylaxis management.