TY - JOUR
T1 - Characterizing Enoxaparin’s Population Pharmacokinetics to Guide Dose Individualization in the Pediatric Population
AU - the Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee
AU - Carreño, Fernando O.
AU - Gerhart, Jacqueline G.
AU - Helfer, Victória E.
AU - Sinha, Jaydeep
AU - Kumar, Karan R.
AU - Kirkpatrick, Carl
AU - Hornik, Christoph P.
AU - Gonzalez, Daniel
AU - Stone, Don
AU - Schwitters, Jeff
AU - Vuyyuri, Satish
AU - Singh, K. P.
AU - Heilman, Steve
AU - Sullivan, Janice
AU - Smith, Michael
AU - Muller, William
AU - Miller, Michael
AU - Clark, Cindy
AU - Talbert, Jennifer
AU - Laughon, Matt
AU - Bow, Peter
AU - Jared, Jeremy
AU - Estill, Jamie
AU - Liamini, Don
AU - Kaleba, Erin
AU - Eickstadt, Richard
AU - Attala, Samara
AU - Gipson, Debbie
AU - Fogel, Benjamin
AU - O’Connor, Shawn
AU - Ramos, Mark
AU - Grundmeier, Robert
AU - Downes, Kevin
AU - Fan, Stephanie
AU - Chan, Francis
AU - Grillo, Sonya
AU - Harvey, Brian
AU - Bendel, Catherine
AU - Chundru, Kalyan
AU - Clark, John
AU - Lenert, Leslie
AU - Atz, Andrew
AU - Green, Terren
AU - Alderman, Cheryl
AU - Greenberg, Rachel
AU - Zimmerman, Kanecia
AU - Capparelli, Edmund
AU - Autmizguine, Julie
AU - Paul, Ian
AU - Anand, Ravinder
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024..
PY - 2024/7
Y1 - 2024/7
N2 - 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).Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct.The author names are accurately presented and the metadata are correct. 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.
AB - 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).Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct.The author names are accurately presented and the metadata are correct. 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.
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U2 - 10.1007/s40262-024-01388-x
DO - 10.1007/s40262-024-01388-x
M3 - Article
C2 - 38955947
AN - SCOPUS:85199818998
SN - 0312-5963
VL - 63
SP - 999
EP - 1014
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
IS - 7
ER -