Related Experiment Video

Updated: Sep 13, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

8.1K

PBPK Modeling of Acetaminophen in Pediatric Populations: Incorporation of SULT Enzyme Ontogeny to Predict

Sonia Sharma1, David R Taft1

  • 1Samuel J. and Joan B. Williamson Institute for Pharmacometrics, Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA.

Life (Basel, Switzerland)
|July 29, 2025
PubMed

Insights

This study developed a PBPK model for acetaminophen (APAP) in pediatric patients, accounting for sulfotransferase (SULT) enzyme development. The model accurately predicts APAP pharmacokinetics, highlighting SULT

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Pediatric Pharmacology
  • Computational Biology

Background:

  • Sulfotransferase (SULT) enzymes are crucial for drug metabolism in pediatric populations.
  • Acetaminophen (APAP) is widely used in children, necessitating understanding its metabolic pathways.
  • Ontogeny of SULT enzymes significantly impacts drug clearance in developing individuals.

Purpose of the Study:

  • To develop a physiologically based pharmacokinetic (PBPK) model for APAP in pediatric populations.
  • To incorporate the developmental ontogeny of key SULT isozymes (SULT1A1, SULT1A3, SULT2A1) into the PBPK model.
  • To evaluate the role of SULT ontogeny in APAP metabolism and potential drug-drug interactions (DDIs).

Main Methods:

  • Utilized the Simcyp® Simulator for PBPK modeling and simulation.
  • Incorporated age-dependent SULT enzyme ontogeny using nonlinear regression analysis.
  • Validated the PBPK model against observed clinical pharmacokinetic data (Cmax, AUC) in neonates, infants, and children.

Main Results:

  • The PBPK model successfully captured APAP's pharmacokinetic profiles across pediatric age groups.
  • SULT enzymes accounted for approximately 60% of APAP metabolism in neonates, decreasing with age.
  • Sensitivity analysis indicated SULT1A1 as a key enzyme for potential APAP metabolic DDIs.

Conclusions:

  • SULT enzyme activity is a significant determinant of APAP metabolism in neonates.
  • The developed PBPK model, incorporating SULT ontogeny, accurately predicts APAP pharmacokinetics in pediatric populations.
  • This model can aid in optimizing APAP dosing strategies for pediatric patients, considering developmental changes in drug metabolism.

Keywords:
PBPK modelingSULTacetaminophenneonatesontogenypediatrics

More Related Videos

Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications07:23

Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications

Published on: October 20, 2023

1.5K
Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration05:37

Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration

Published on: May 31, 2018

12.3K

Related Concept Videos

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
82
Pharmacokinetic Models: Overview01:20

Pharmacokinetic Models: Overview

Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
1.1K
Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
150
Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis00:59

Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis

Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
126
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...
299
Analysis of Population Pharmacokinetic Data01:12

Analysis of Population Pharmacokinetic Data

Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
387