Characterizing Enoxaparin's Population Pharmacokinetics to Guide Dose Individualization in the Pediatric Population.

BACKGROUND AND

OBJECTIVE

Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population pharmacokinetics (PopPK)

METHODS

A PopPK analysis was performed using NONMEM, and a stepwise covariate modeling approach was applied for the covariate selection. The final PopPK model, developed with data from 1293 patients ranging in age from 1 day to 18 years, was used to simulate enoxaparin subcutaneous dosing for prophylaxis and treatment based on total body weight (0-18 years, TBW) or fat-free mass (2-18 years, FFM). Simulated exposures in children with obesity (body mass index percentile ≥95th percentile) were compared with those without obesity.

RESULTS

A linear, one-compartment PopPK model that included allometric scaling using TBW (<2 years) or FFM (≥2 years) characterized the enoxaparin pharmacokinetic data. In addition, serum creatinine was identified as a significant covariate influencing clearance. Simulations indicated that in patients aged <2 years, the recommended 1.5 mg/kg TBW-based dosing achieves therapeutic simulated concentrations. In pediatric patients aged ≥2 years, the recommended 1.0 mg/kg dose resulted in exposures more comparable in children with and without obesity when FFM weight-based dosing was applied.

CONCLUSION

Using real-world data and PopPK modeling, enoxaparin's pharmacokinetics were characterized in pediatric patients. Using FFM and twice-daily dosing might reduce the risk of overdosing, especially in children with obesity.