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Related Concept Videos

Toxicokinetics: Overview01:21

Toxicokinetics: Overview

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Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
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Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

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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.
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Toxic Reactions: Overview01:26

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When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
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Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

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Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
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Pharmacokinetic–Pharmacodynamic Relationship: Problems01:24

Pharmacokinetic–Pharmacodynamic Relationship: Problems

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The empirical approach to drug therapy optimization relies on correlating pharmacological response with administered dosage. Such an approach can be costly, time-consuming, and often yields poor correlation due to variables like formulation factors and drug elimination characteristics. A more precise approach correlates response with plasma drug concentration or the amount of drug in the body, rather than dosage. This is achieved through pharmacokinetic-pharmacodynamic (PK/PD) modeling, which...
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Toxicity Testing in Animals01:23

Toxicity Testing in Animals

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Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
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Related Experiment Video

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A toxicity cost function approach to optimal CPA equilibration in tissues.

James D Benson1, Adam Z Higgins2, Kunjan Desai3

  • 1Department of Biology, University of Saskatchewan, Canada.

Cryobiology
|October 3, 2017
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Developing new computational models for tissue cryopreservation is crucial for transplantation and regenerative medicine. This study optimizes cryoprotective agent (CPA) protocols, showing that tailored approaches minimize toxicity and time, unlike one-size-fits-all methods.

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Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Cryobiology

Background:

  • Cryopreservation of tissues is vital for transplantation and regenerative medicine.
  • Current cryopreservation methods lack uniformity and struggle with arbitrary tissue types.
  • Computational models for tissue cryopreservation have historically been limited to explanatory approaches.

Purpose of the Study:

  • To develop a numerical approach for optimizing tissue cryopreservation protocols.
  • To adapt cell-based cryoprotective agent (CPA) equilibration damage models for tissue mass transport.
  • To minimize cell-based cumulative toxicity and osmotic gradient damage during tissue cryopreservation.

Main Methods:

  • Measured CPA (propylene glycol) diffusivity in human skin, fibroid, and myometrium tissues.
  • Developed a numerical model integrating CPA diffusivity with tissue mass transport.
  • Predicted and compared optimal multistep CPA equilibration protocols using computational simulations.

Main Results:

  • Propylene glycol diffusivities were determined for skin (0.6 × 10⁻⁶ cm²/s), fibroid (1.2 × 10⁻⁶ cm²/s), and myometrium (1.3 × 10⁻⁶ cm²/s).
  • Numerical predictions revealed distinct optimal protocols for minimizing CPA exposure time versus minimizing CPA toxicity.
  • "One size fits all" stepwise protocols are predicted to be less efficient and more toxic than tailored approaches.

Conclusions:

  • Tailored, multi-step CPA equilibration protocols are superior to uniform approaches for tissue cryopreservation.
  • Computational modeling provides a powerful tool for optimizing cryopreservation strategies.
  • This work advances the development of effective cryopreservation techniques for transplantation and regenerative medicine.