Related Experiment Video

Updated: Jun 4, 2025

Transdermal Measurement of Glomerular Filtration Rate in Mechanically Ventilated Piglets
07:41

Transdermal Measurement of Glomerular Filtration Rate in Mechanically Ventilated Piglets

Published on: September 13, 2022

3.1K

Population Pharmacokinetics of Trofinetide in a Pediatric Population Aged 2-4 Years with Rett Syndrome

Mona Darwish1, Julie Passarell2, Kelly Maxwell2

  • 1Acadia Pharmaceuticals Inc., 12830 El Camino Real, Suite 400, San Diego, CA, 92130, USA. mdarwish@ACADIA-Pharm.com.

Advances in Therapy
|December 18, 2024
PubMed

Insights

Weight-banded trofinetide dosing in young Rett syndrome patients (2-4 years) achieves target drug exposure. This confirms the DAFFODIL study

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Pediatric Pharmacology
  • Neurology and Neurodevelopmental Disorders

Background:

  • Trofinetide dosing regimens were previously established using population pharmacokinetic (popPK) modeling and simulations for Rett syndrome (RTT) patients aged 2-20 years.
  • Weight-banded dosing demonstrated improved efficacy and acceptable tolerability in the DAFFODIL (2-4 years) and LAVENDER (5-20 years) studies.
  • This study aimed to validate trofinetide exposures in the youngest RTT cohort using an updated popPK model.

Purpose of the Study:

  • To confirm that the weight-banded trofinetide dosing regimen used in the DAFFODIL study achieves target steady-state exposures in pediatric patients aged 2-4 years with Rett syndrome.
  • To utilize an updated population pharmacokinetic model to analyze trofinetide exposure levels in young RTT patients.

Main Methods:

  • A comprehensive popPK model was developed incorporating data from 14 clinical studies involving healthy volunteers and patients with RTT.
  • Individual steady-state exposure (AUC0-12) for DAFFODIL participants was calculated using the popPK model and Bayesian pharmacokinetic parameter estimates.
  • Simulated AUC0-12 values were compared against the established target exposure range of 800–1200 µg·h/mL.

Main Results:

  • Simulations of steady-state AUC0-12 values for the weight-banded trofinetide dosing regimen in 2- to 4-year-old RTT patients showed good overlap with the target exposure range.
  • The median steady-state AUC0-12 values for both weight bands (5g for 9-<12kg, 6g for 12-<20kg) fell within the therapeutic target range.
  • The weight-banded dosing strategy effectively achieved desired trofinetide exposure levels in the youngest RTT patient group.

Conclusions:

  • Population pharmacokinetic modeling and simulation confirm that the weight-banded dosing regimen employed in the DAFFODIL study is adequate for achieving target trofinetide exposure in 2- to 4-year-old patients with Rett syndrome.
  • These findings support the continued use of weight-banded dosing for trofinetide in pediatric RTT populations.
Abstract

Keywords:
DAFFODIL studyPopulation pharmacokinetic modelingRett syndromeTrofinetideWeight-banded dosing regimen

More Related Videos

Transcutaneous Assessment of Renal Function in Conscious Rodents07:18

Transcutaneous Assessment of Renal Function in Conscious Rodents

Published on: March 26, 2016

12.4K
Radiosynthesis of 1-2-[18F]Fluoroethyl-L-Tryptophan using a One-pot, Two-step Protocol08:33

Radiosynthesis of 1-2-[18F]Fluoroethyl-L-Tryptophan using a One-pot, Two-step Protocol

Published on: September 21, 2021

3.0K

Related Concept Videos

Renal Failure: Dose Adjustments01:11

Renal Failure: Dose Adjustments

In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
63
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
80
Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
1.8K
Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
2.5K