Back to Basics: Understanding Drugs in Children: Pharmacokinetic Maturation
Bibliographic record
Abstract
1. Maria Tetelbaum, MD* 2. Yaron Finkelstein, MD* 3. Alejandro A. Nava-Ocampo, MD* 4. Gideon Koren, MD* 1. *Division of Clinical Pharmacology & Toxicology, Department of Pediatrics and Population Health Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada After completing this article, readers should be able to: 1. Recognize age-related changes in pharmacokinetics and pharmacodynamics of drugs. 2. Describe the dynamics of rational drug dosing for neonates and children. 3. Identify areas of challenge where more drug research is needed during development. Rapid age-related physiologic changes in the pediatric age group, especially during the first postnatal year, affect the absorption, distribution, metabolism, and elimination of drugs. This article reviews pharmacokinetic principles in neonates, infants, and children to help pediatricians understand the rationale for drug therapy and toxicity in these patients. Drugs are administered through a wide range of routes (Table 1). General pharmacokinetic and pharmacodynamic principles can be defined by grouping them in two major routes: intravascular and extravascular. Extravascular administration entails absorption, distribution, metabolism, and excretion. Bioavailability is the fraction of drug reaching the systemic circulation following its administration by any route. Because drugs administrated intravenously do not require an absorption process, their bioavailability is 100%. | Intravascular | || | Extravascular | | Less Common: | Table 1. Primary Routes of Drug Absorption in Children ### Oral Administration Among the extravascular routes, oral administration commonly is used not only because it is painless, but also because technology involved in oral formulations is relatively less costly and requires fewer pharmaceutical processes. However, in some cases, the choice of administration route depends on the site of action, the desired plasma drug concentrations, and the time at which a certain drug concentration must be achieved. Bioavailability after oral administration naturally is less than after intravenous administration. The primary factors affecting oral bioavailability are listed in Table 2. | Physicochemical Factors | || | Physiologic Factors |
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.014 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.004 | 0.009 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.010 |
| Insufficient payload (model declined to judge) | 0.008 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".