Related Experiment Video

Updated: Apr 5, 2026

Author Spotlight: Exploring Venous Waveforms in Porcine Models to Tackle Volume Overload in Medicine
06:09

Author Spotlight: Exploring Venous Waveforms in Porcine Models to Tackle Volume Overload in Medicine

Published on: January 12, 2024

1.1K

Extrapolation of enalapril efficacy from adults to children using pharmacokinetic/pharmacodynamic modelling

Irene-Ariadne Kechagia1, Lida Kalantzi2, Aristides Dokoumetzidis1

  • 1School of Pharmacy, University of Athens, Athens, Greece.

The Journal of Pharmacy and Pharmacology
|August 11, 2015
PubMed

Insights

Mathematical modeling successfully predicted enalapril efficacy in children aged 0-6 years. This pharmacokinetic/pharmacodynamic (PKPD) model supports pediatric drug development for enalapril.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Mathematical Modeling

Background:

  • Enalapril efficacy data in young children (0-6 years) is limited.
  • Pharmacokinetic/pharmacodynamic (PKPD) modeling can predict drug efficacy across age groups.
  • Accurate dosing in pediatric populations is crucial for treatment effectiveness.

Purpose of the Study:

  • To develop and validate a PKPD model for enalapril.
  • To extrapolate enalapril efficacy to children aged 0-6 years.
  • To support a pediatric investigation plan for enalapril.

Main Methods:

  • A two-compartment PK model was developed using pediatric data up to 16 years.
  • An indirect link PD model was fitted to adult data.
  • The PKPD model was validated using efficacy data in children aged 6 years and older.

Main Results:

  • The PK model incorporated weight as a covariate for clearance and central volume.
  • The PKPD model successfully predicted enalapril efficacy in children.
  • Extrapolated mean diastolic blood pressure (DBP) drop was 11.2 mmHg for infants (1-11 months) and 11.79 mmHg for children (1-6 years).

Conclusions:

  • Mathematical modeling provides a reliable method for extrapolating enalapril efficacy to young children.
  • The validated PKPD model supports the pediatric investigation plan for enalapril.
  • Findings aid in pursuing a pediatric-use marketing authorization application.
Abstract

Keywords:
enalaprilpaediatric investigation planpharmacokinetic/pharmacodynamic extrapolation

More Related Videos

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion09:02

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion

Published on: February 2, 2021

5.0K
Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

10.3K

Related Concept Videos

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions01:15

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure...
72
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
341
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
378
Drug Dosing: Infants and Children01:29

Drug Dosing: Infants and Children

Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
804
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
484
Pharmacokinetic–Pharmacodynamic Relationship: Problems01:24

Pharmacokinetic–Pharmacodynamic Relationship: Problems

The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
88