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Related Concept Videos

Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model01:14

Pharmacodynamic Models: Link Model and Systems Pharmacodynamic Model

The link model is a fundamental pharmacokinetic-pharmacodynamic (PK–PD) approach to account for delayed drug responses when the observed effect does not immediately correlate with the drug's plasma concentration peak. This delay is mathematically addressed by introducing an effect compartment concentration, Ce, which is kinetically linked to the plasma concentration, Cp, via a first-order rate constant, ke0. The linkage allows for a more accurate prediction of drug effects over time. A higher...
Compartment Models: Two-Compartment Model01:20

Compartment Models: Two-Compartment Model

The two-compartment model divides the body into central and peripheral compartments to account for varying blood perfusion rates among organs and tissues, affecting drug distribution. The central compartment includes blood and highly perfused tissues with rapid drug distribution, while the peripheral compartment contains tissues with slower drug distribution. After a single IV bolus dose, the drug concentration is high in plasma and low in tissues. The drug distribution between compartments...
Pharmacodynamic Models: Additive and Proportional Drug Effect Model01:09

Pharmacodynamic Models: Additive and Proportional Drug Effect Model

Drug response models describe how pharmacological agents interact with biological systems to produce measurable effects. Baseline responses are inherent physiological activities without a drug significantly influencing the observed pharmacological outcomes. Depending on the drug response model employed, these baseline responses may combine with the drug's effect in either an additive or proportional manner.Additive Drug Response ModelIn the additive model, the drug effect is independent of the...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
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 assumptions,...
Three-Compartment Open Model01:06

Three-Compartment Open Model

The three-compartment open model is a pharmacokinetic model used to describe the distribution and elimination of drugs following extravascular administration. It comprises a central compartment representing the plasma and two peripheral compartments. The highly perfused peripheral compartment represents organs and tissues with a rich blood supply, such as the liver, kidneys, and lungs. The scarcely perfused peripheral compartment represents tissues with lower blood supply, such as adipose...

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Related Experiment Video

Updated: Jul 1, 2026

Fentanyl Analog Screening using LC-TIMS-TOF MS/MS
10:13

Fentanyl Analog Screening using LC-TIMS-TOF MS/MS

Published on: November 8, 2024

A 4-zone model to determine fentanyl overdose probability.

Manolo U Rios1, Jessica B Dwyer2, Sara K Dempsey2

  • 1Department of Pathology, UT Southwestern Medical Center, Dallas, Texas, USA.

Journal of Forensic Sciences
|June 30, 2026
PubMed
Summary
This summary is machine-generated.

Forensic toxicologists can now objectively determine overdose certainty using a new statistical model for postmortem fentanyl blood concentrations. This model aids in distinguishing overdose deaths from incidental findings, improving accuracy in cause of death investigations.

Keywords:
femoral bloodfentanylforensic toxicologyoverdosepostmortemprobability and distribution analysis

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Area of Science:

  • Forensic toxicology
  • Toxicological analysis
  • Postmortem drug testing

Background:

  • Determining cause of death from postmortem fentanyl concentrations is challenging due to overlapping values in overdose vs. incidental cases.
  • Current literature lacks objective frameworks for interpreting fentanyl concentrations, relying on descriptive statistics like ranges and medians.
  • Existing methods fail to provide a robust evaluation of the evidentiary value of specific fentanyl levels.

Purpose of the Study:

  • To develop a statistically rigorous and objective method for quantifying overdose probability using postmortem femoral blood fentanyl concentrations.
  • To assess the impact of polysubstance use on overdose probability and adjust interpretive windows accordingly.
  • To identify demographic and drug class factors influencing overdose classification.

Main Methods:

  • Utilized distribution analysis, nonparametric tests, and likelihood ratios to create a four-zone statistical model.
  • Employed logistic regression modeling to evaluate the influence of age, sex, and co-administered drug classes.
  • Analyzed data to determine how polysubstance use modifies overdose probability calculations.

Main Results:

  • Developed a four-zone statistical model to quantify postmortem overdose probability based on femoral blood fentanyl levels.
  • Demonstrated that polysubstance use significantly alters overdose probabilities, necessitating adjusted interpretive windows.
  • Logistic regression indicated minimal contribution from age and sex, while identifying key drug classes for overdose prediction.

Conclusions:

  • The study presents a rigorous, objective statistical model for determining postmortem overdose certainty in fentanyl-related deaths.
  • The model provides a framework for interpreting fentanyl concentrations, accounting for polysubstance use and improving diagnostic accuracy.
  • This approach enhances the evidentiary value of toxicological findings in forensic investigations of drug intoxication.