Related Experiment Video
Updated: Jun 9, 2025
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Drug dosing optimization in critically ill children under continuous renal replacement therapy: from basic concepts
Mehdi Oualha1,2, Michael Thy2,3, Naïm Bouazza2
1Pediatric Intensive Care Unit, Necker Hospital, APHP-Centre, Université of Paris-Cité, Paris, France.
Insights
Optimizing drug dosage for critically ill children on Continuous Renal Replacement Therapy (CRRT) is complex. Model-informed precision dosing and therapeutic drug monitoring can aid in personalized pediatric CRRT drug regimens.
Area of Science:
- Pediatric Critical Care Pharmacology
- Renal Replacement Therapy
- Pharmacokinetic Modeling
Background:
- Drug dosage optimization in critically ill children receiving Continuous Renal Replacement Therapy (CRRT) presents significant challenges due to pharmacokinetic and pharmacodynamic variability.
- Understanding drug elimination mechanisms during CRRT is crucial for avoiding prescription errors, despite high inter- and intra-patient variability.
Purpose of the Study:
- To review the current understanding and methodologies for optimizing drug dosage in pediatric patients undergoing CRRT.
- To highlight the role of advanced modeling techniques in achieving precision dosing.
Main Methods:
- A systematic literature search was conducted in PubMed using specific keywords related to pediatric CRRT, pharmacokinetics, modeling, and therapeutic drug monitoring.
- The search included studies published until January 2024, irrespective of language or publication status.
Main Results:
- Population pharmacokinetic and physiologically based pharmacokinetic models are essential tools for suggesting adjusted dosage regimens.
- These models, derived from in-vivo and in-vitro studies, are challenging but remain the most appropriate approach for individualized dosing.
Conclusions:
- Educating pediatric intensivists on therapeutic drug monitoring and implementing individualized prescribing software like Model Informed Precision Dosing is a critical advancement.
- Further clinical studies are required to definitively demonstrate the patient benefit of these precision dosing strategies.
Introduction:
Optimizing drug dosage in critically ill children undergoing Continuous Renal Replacement Therapy (CRRT) is mandatory and challenging, given the many factors impacting pharmacokinetics and pharmacodynamics coupled with the vulnerability of this population.
Areas Covered:
A good understanding of the mechanisms that determine drug elimination via the CRRT technique is useful to avoid prescription pitfalls, however limited by the high between and within subject variability. The developments of population pharmacokinetic and physiologically based pharmacokinetic models derived from in-vivo and in-vitro studies, are challenging, but remain the most appropriate tool to suggest adjusted dosage regimens for every patient, throughout treatment. We searched PubMed using the search string: 'pediatrics OR children' AN 'continuous renal replacement therapy' AND 'pharmacokinetics' AND 'model informed precision dosing' AND, 'physiologically based pharmacokinetics,' AND 'therapeutic drug monitoring' until January 2024, regardless of language or publication status.
Expert Opinion:
Familiarizing the pediatric intensivists with the therapeutic drug monitoring and providing clinicians the individualized prescribing software such as Model Informed Precision Dosing would be a significant step forward. The clinical benefit for patients remains to be demonstrated.
Related Concept Videos
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...
01:24Rational 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...
01:09One-Compartment Model: IV Infusion
The one-compartment model for IV infusion uses mathematical equations to describe the rate of change in drug quantity in the body. At steady-state or infusion equilibrium, the drug input...
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...
01:21Factors Affecting Drug Response: Overview
01:26Pharmacokinetic Models: Comparison and Selection Criterion
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.