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Related Concept Videos

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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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Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
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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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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Microphysiological Systems to Assess Nonclinical Toxicity.

Kirk P Van Ness1, Shih-Yu Chang2, Elijah J Weber1

  • 1Department of Pharmaceutics, University of Washington, Seattle, Washington.

Current Protocols in Toxicology
|August 5, 2017
PubMed
Summary

This study introduces a novel microphysiological system (MPS) platform for improved drug toxicity testing. The renal and hepatic MPS platform better maintains cell function for more accurate toxicology investigations.

Keywords:
hepatocytein vitro modelsmicrophysiological systemsproximal tubule

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Area of Science:

  • Toxicology
  • Drug Development
  • In Vitro Models

Background:

  • Liver and kidney are primary drug toxicity targets.
  • Traditional 2-D cell cultures lack essential metabolic and transport functions.
  • This limits their use in nonclinical toxicology.

Purpose of the Study:

  • To develop a renal and hepatic microphysiological system (MPS) platform.
  • To improve in vitro models for drug toxicity assessment.
  • To better recapitulate human kidney and liver functions.

Main Methods:

  • Utilized a commercially available MPS device.
  • Developed protocols for isolating and culturing human proximal tubule epithelial cells.
  • Established methods for culturing hepatocytes and connecting renal and liver MPS.

Main Results:

  • Successfully cultured human proximal tubule epithelial cells in a renal MPS.
  • Established two methods for hepatocyte culture within an MPS.
  • Demonstrated the ability to connect renal and hepatic MPS modules.

Conclusions:

  • The developed MPS platform enhances the maintenance of critical cell functions.
  • This system offers a more predictive model for drug-induced liver and kidney toxicity.
  • The platform advances in vitro toxicology for drug development.