Related Experiment Video

Updated: May 7, 2026

A Point-of-Care Method with Integrated Decision Support Tool to Estimate Anemia at Population Level
05:35

A Point-of-Care Method with Integrated Decision Support Tool to Estimate Anemia at Population Level

Published on: January 19, 2024

Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging

Mallika Lala1, Gilbert J Burckart, Cheryl M Takao

  • 1Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland ; School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia.

The Journal of Pediatric Pharmacology and Therapeutics : JPPT : the Official Journal of PPAG
|September 21, 2013
PubMed

Insights

A new warfarin dosing regimen for children was developed using genetic information. This genetics-based approach aims to improve warfarin dosing accuracy and therapeutic outcomes in pediatric patients.

Area of Science:

  • Pharmacogenomics
  • Pediatric pharmacology
  • Drug dosing optimization

Background:

  • Warfarin dosing in adults is guided by CYP2C9 and VKORC1 genetic polymorphisms, as recognized by the FDA.
  • No established genetic-based dosing algorithm currently exists for pediatric patients.

Purpose of the Study:

  • To develop a genetics-based warfarin dosing regimen for pediatric patients.
  • The regimen includes both an initial starting dose and a titration scheme.

Main Methods:

  • A model-based approach adapted from an established adult warfarin dosage model.
  • Pediatric data from 26 subjects at Children's Hospital of Los Angeles were used for comparison.
  • Genotyping focused on CYP2C9 variant alleles (*2, *3) and the VKORC1 rs9923231 SNP.

Main Results:

  • A validated pediatric warfarin dosage model was derived.
  • Simulations and stochastic modeling optimized the pediatric dosage and titration strategy.
  • The optimized regimen targets a high proportion of international normalized ratios (INRs) within the therapeutic range by week 2.

Conclusions:

  • The proposed genetics-based warfarin dosage scheme, considering CYP2C9 and VKORC1 genotypes, may enhance pediatric dosing.
  • This pilot study lays the groundwork for future prospective evaluations of genetic-guided warfarin therapy in children.
Abstract

Keywords:
CYP2C9VKORC1pediatricspharmacogeneticswarfarin

Related Concept Videos

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...
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
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, compared...
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...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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 a challenge in...