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Clinical pharmacokinetics in infants and children. A reappraisal
1Division of Pediatric Infectious Disease, Clinical Pharmacology (Arkansas Children's Hospital), Little Rock.
Insights
Paediatric clinical pharmacology has advanced, but drug effects in children are not fully understood. This review highlights developmental differences in drug disposition and pharmacodynamics for better paediatric therapeutics.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Paediatric Therapeutics
Background:
- Paediatric clinical pharmacology knowledge has grown significantly in the last 20 years.
- Despite increased data on drug disposition in children, pharmacokinetic-pharmacodynamic interactions, especially developmental effects, remain poorly understood.
- Key differences in drug disposition between neonates, infants, children, and adults involve body composition and hepatic metabolism.
Purpose of the Study:
- To review the impact of developmental physiology on drug absorption, distribution, metabolism, and elimination in infants and children.
- To contrast these factors with determinants of clinical pharmacokinetics in neonates.
- To highlight developmental pharmacology differences through controversies in paediatric drug use.
Main Methods:
- Review of existing literature on drug disposition and pharmacokinetics in paediatric populations.
- Contrast of pharmacokinetic determinants in neonates, infants, children, and adults.
- Examination of specific paediatric pharmacokinetic-pharmacodynamic controversies and clinical evaluation considerations.
Main Results:
- Notable differences in drug disposition are linked to body water, serum protein composition, and hepatic biotransformation capacity.
- Developmental pharmacology is illustrated by controversies in cystic fibrosis, bacterial meningitis antimicrobial therapy, and cyclosporine immunosuppression.
- Clinical pharmacokinetic evaluations require specific considerations for drug administration, sampling, and mathematical techniques in paediatric patients.
Conclusions:
- Clinical pharmacokinetics serves as a crucial link between research and clinical practice in paediatrics.
- Understanding developmental pharmacology is essential for optimizing drug therapy and research in infants and children.
- Pharmacokinetics offers a valuable tool for paediatric research, clinical care, and even forensic applications.
Abstract:
A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics. Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood. The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates. The most notable differences in drug disposition between infants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics. As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children. These include the issues of altered drug distribution and metabolism in cystic fibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin. The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies. Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge. Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care. The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients. Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data.