Related Experiment Video
Updated: Sep 5, 2025
Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood
Published on: October 12, 2012
Optimal dosing of enoxaparin in overweight and obese children
Abdallah Derbalah1, Stephen Duffull1, Catherine M Sherwin2
1School of Pharmacy, University of Otago, Dunedin, New Zealand.
Insights
Current enoxaparin dosing for children may be inaccurate for obese patients. This study developed a new fat-free mass-based dosing regimen to improve therapeutic effectiveness in pediatric patients receiving enoxaparin.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Pharmacokinetics
Background:
- Current enoxaparin dosing in children relies on total body weight, which may lead to inaccurate drug clearance in obese pediatric patients.
- Obese children might require adjusted enoxaparin doses to achieve therapeutic efficacy.
Purpose of the Study:
- To characterize the pharmacokinetics of enoxaparin in obese children.
- To propose an optimized enoxaparin dosing regimen for pediatric patients, particularly those who are overweight or obese.
Main Methods:
- Analysis of data from 160 children (196 encounters) treated with enoxaparin.
- Quantification of enoxaparin concentration using the chromogenic anti-factor Xa (anti-Xa) assay.
- Development of a population pharmacokinetic (PK) model using nonlinear mixed-effects modeling, incorporating fat-free mass as a covariate.
Main Results:
- Existing pediatric enoxaparin PK models were inadequate for obese children.
- Fat-free mass was identified as a key covariate influencing enoxaparin clearance and volume of distribution.
- Simulations indicated that fat-free mass-based dosing improved target anti-Xa activity attainment compared to total body weight-based dosing in both obese and normal-weight children.
Conclusions:
- A population PK model for enoxaparin in children was developed.
- A unified, fat-free mass-based dosing regimen is proposed to enhance target anti-Xa activity attainment in overweight/obese pediatric patients.
- Prospective validation of the proposed dosing strategy is recommended.
Aim:
Current enoxaparin dosing guidelines in children are based on total body weight. This is potentially inappropriate in obese children as it may overestimate the drug clearance. Current evidence suggests that obese children may require lower initial doses of enoxaparin, therefore the aim of this work was to characterise the pharmacokinetics of enoxaparin in obese children and to propose a more appropriate dosing regimen.
Methods:
Data from 196 unique encounters of 160 children who received enoxaparin treatment doses were analysed. Enoxaparin concentration was quantified using the chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted and evaluated against our dataset using prediction-corrected visual predictive check plots (pcVPCs). A PK model was fitted using a nonlinear mixed-effects modelling approach. The fitted model was used to evaluate the current standard dosing and identify an optimal dosing regimen for obese children.
Results:
Published models of enoxaparin pharmacokinetics in children did not capture the pharmacokinetics of enoxaparin in obese children as shown by pcVPCs. A one-compartment model with linear elimination best described the pharmacokinetics of enoxaparin. Allometrically scaled fat-free mass with an estimated exponent of 0.712 (CI 0.66-0.76) was the most influential covariate on clearance while linear fat-free mass was selected as the covariate on volume. Simulations from the model showed that fat-free mass-based dosing could achieve the target anti-Xa activity at steady state in 77.5% and 78.2% of obese and normal-weight children, respectively, compared to 65.2% and 75.5% for standard total body weight-based dosing.
Conclusions:
A population PK model that describes the time course of anti-Xa activity of enoxaparin was developed in a paediatric population. Based on this model, a unified dosing regimen was proposed that will potentially improve the success rate of target attainment in overweight/obese patients without the need for patient body size categorisation. Therefore, prospective validation of the proposed approach is warranted.
Related Concept Videos
01:16Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
01:21Factors Affecting Drug Response: Overview
01:24Rational Dosage Regimen: Maintenance Dose and Loading Dose
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:15Drug Dosage Regimen: Overview
Typically, the starting dose and dosing interval are guided by the manufacturer's recommendations based on clinical trials conducted during and after drug...