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Understanding dosing: children are small adults, neonates are immature children
Brian J Anderson1, Nick H G Holford
1Department of Anaesthesiology, University of Auckland, Auckland, New Zealand. briana@adhb.govt.nz
Insights
Paediatric drug dosing requires more than simple weight scaling. Understanding drug concentration-response (pharmacodynamics) and how the body processes drugs (pharmacokinetics) is crucial for safe and effective paediatric medication.
Area of Science:
- Pharmacology
- Paediatric Medicine
- Drug Development
Background:
- Direct scaling of adult drug doses by weight is inappropriate for paediatric patients.
- Infants and neonates have immature drug elimination pathways, leading to altered drug responses.
- Accurate paediatric dosing requires consideration of pharmacokinetics and pharmacodynamics.
Purpose of the Study:
- To highlight the challenges in paediatric drug dosing.
- To emphasize the importance of pharmacokinetics and pharmacodynamics in determining appropriate paediatric doses.
- To advocate for more paediatric pharmacodynamic studies.
Main Methods:
- Review of pharmacokinetic and pharmacodynamic principles in paediatric drug dosing.
- Discussion of variability factors including size, maturation, and organ function.
- Analysis of the limitations of weight-based dosing in children.
Main Results:
- Paediatric drug dosing is complex due to immature elimination pathways in neonates and infants.
- Children over two years old generally have mature drug elimination similar to adults, differing mainly in size.
- Pharmacokinetic and pharmacodynamic variability can be mitigated using demographic covariates.
- A significant lack of paediatric pharmacodynamic studies hinders rational dosing strategies.
Conclusions:
- Rational paediatric drug dosing necessitates understanding both pharmacokinetics and pharmacodynamics.
- Demographic factors like size and maturation are critical for individualizing paediatric doses.
- Further paediatric pharmacodynamic research is essential for optimizing treatment outcomes and ensuring patient safety.
Abstract:
Paediatric dose cannot be scaled down directly from an adult using weight (eg, mg/kg). This results in a dose too small in infants and children because elimination does not change in direct proportion to weight, and a dose too large in neonates whose drug elimination pathways are immature. The goal of treatment is a desired response (the target effect). An understanding of the concentration-response relationship (pharmacodynamics) can be used to predict the target concentration required to achieve this target effect. Pharmacokinetic knowledge then determines the target dose that will achieve the target concentration. Variability associated with both pharmacokinetics and pharmacodynamics can be reduced by demographic information (covariates), which can be used to help predict the target dose in a specific child. The covariates of size, maturation and organ function are the three principle contributors to pharmacokinetic variability. Children (2 years postnatal age or older) are essentially similar to adults (ie, mature) and differ only in size. Maturation processes are only important in neonates and infants, therefore, this cohort can be viewed as immature children. Paediatric pharmacodynamic studies are fewer than pharmacokinetic studies, but are required to elucidate the target concentration and consequent dose. The lack of pharmacodynamic studies is a serious challenge for rational dosing.
Related Concept Videos
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01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:21Factors Affecting Drug Response: Overview
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism