# Is the current therapeutic dosage of nadroparin adequate for neonates and infants under 8 months with thromboembolic disease? a population pharmacokinetic study from a national children’s medical center

## TL;DR

This study finds that the current dosage of nadroparin may be too low for neonates and infants under 8 months, suggesting higher doses might be needed for effective treatment.

## Contribution

The study provides the first population pharmacokinetic model for nadroparin in neonates and infants under 8 months.

## Key findings

- Current therapeutic doses of nadroparin may result in subtherapeutic exposure in neonates and infants.
- Creatinine clearance significantly affects inter-individual variability in drug clearance.
- A one-compartment model best fits the pharmacokinetic data of nadroparin in this population.

## Abstract

Objectives: Nadroparin, a low-molecular-weight-heparin is commonly used off-label in neonates and infants for thromboembolic events prevention. However, the recommended dosing regimen often fails to achieve therapeutic target ranges. This study aimed to develop a population pharmacokinetic (PK) model of nadroparin to determine an appropriate dosing regimen for neonates and infants less than 8 months.

Methods: A retrospective chart review was conducted on patients treated with nadroparin at Children’s Hospital of Fudan University between July 2021 and December 2023. A population PK model was developed using anti-Xa levels, and its predictive performance was evaluated internally. Monte Carlo simulations were performed to design an initial dosing schedule targeting anti-Xa levels between 0.5 and 1 IU/mL.

Results: A total of 40 neonates and infants aged less than 8 months with gestational age ranging from 25 to 41 weeks treated with nadroparin were enrolled in the study for analysis. A one-compartment PK model with first order absorption and elimination was adequately fitted to the data. Creatinine clearance was identified as a significant factor contributing to inter-individual variability in clearance. The typical population parameter estimates of clearance, distribution volume and absorption rate in this population were 0.211 L/h, 1.55 L and 0.495 h-1, respectively. Our findings suggest that current therapeutic doses of nadroparin (150–200 IU/kg q12 h) may result in subtherapeutic exposure, thus higher doses might be required.

Conclusion: The present study offers the first estimation of PK parameters for nadroparin in preterm or term neonates and infants less than 8 months utilizing the model. Our findings have potential implications for recommending initial personalized dosages, particularly among patient populations exhibiting similar characteristics.