Related Experiment Video

Updated: Jul 7, 2025

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies
06:27

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies

Published on: January 10, 2025

755

Physiologically-based pharmacokinetic model for evaluating gender-specific exposures of N-nitrosodimethylamine (NDMA)

Dong Wook Kang1, Ju Hee Kim1, Go-Wun Choi1

  • 1College of Pharmacy, CHA University, 335 Pangyo-Ro, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13488, Republic of Korea.

Archives of Toxicology
|December 21, 2023
PubMed

Insights

This study developed a physiologically-based pharmacokinetic (PBPK) model to understand N-nitrosodimethylamine (NDMA) exposure in rats. The model links NDMA blood concentrations to toxicity, aiding risk assessment for human carcinogen exposure.

Area of Science:

  • Toxicology
  • Pharmacokinetics
  • Biomedical Engineering

Background:

  • N-nitrosodimethylamine (NDMA) is a known human carcinogen with limited data correlating exposure levels with toxicity.
  • Understanding the relationship between NDMA exposure and its effects in target tissues is crucial for risk assessment.

Purpose of the Study:

  • To develop and validate a physiologically-based pharmacokinetic (PBPK) model for N-nitrosodimethylamine (NDMA) in rats.
  • To evaluate gender-specific toxicokinetics, tissue distribution, and excretion of NDMA.
  • To establish a basis for correlating in vivo NDMA exposure with toxicological effects.

Main Methods:

  • Oral administration of three NDMA doses to rats.
  • Development of a PBPK model incorporating major target tissues (blood, GI tract, liver, kidney, lung, heart, brain).
  • Model validation via sensitivity analysis, fold error, and visual inspection; Monte Carlo simulation for variability assessment.

Main Results:

  • A validated PBPK model was successfully developed for NDMA in rats.
  • The model simulates NDMA exposure across acute, intermediate, and chronic durations.
  • Gender-specific pharmacokinetic and toxicokinetic parameters were evaluated.

Conclusions:

  • The developed PBPK model provides a tool to estimate NDMA blood concentration ranges associated with health effects.
  • This research offers a scientific foundation for interpreting the link between NDMA exposure and observed toxicity.
  • The findings support improved risk assessment and management strategies for NDMA contamination.
Keywords:
Monte Carlo simulationN-nitrosodimethylamine (NDMA)Physiologically-based pharmacokinetic (PBPK) modelTissue distributionToxicokinetics

More Related Videos

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s07:38

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

Published on: September 25, 2017

10.1K
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease08:09

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

Published on: January 7, 2014

7.6K

Related Concept Videos

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...
66
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.
74
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,...
40
Model Approaches for Pharmacokinetic Data: Physiological Models01:15

Model Approaches for Pharmacokinetic Data: Physiological Models

Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
47
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...
706
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models01:06

Model Approaches for Pharmacokinetic Data: Distributed Parameter Models

Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
71