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Related Concept Videos

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions01:15

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).
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The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response relationships...

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Related Experiment Video

Updated: Jun 3, 2026

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
06:51

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291

Published on: December 10, 2016

Development and Application of a Novel Dose-Response Model for the Quantification of Clostridioides difficile

Elizabeth N Paddy1, M Sohail1, Oluwasola O D Afolabi1

  • 1School of Architecture, Building and Civil Engineering, Loughborough University, Loughborough, Leicestershire, UK.

Risk Analysis : an Official Publication of the Society for Risk Analysis
|June 2, 2026
PubMed
Summary

A new mouse model provides a dose-response relationship for Clostridioides difficile infection (CDI). This advances quantitative microbial risk assessment (QMRA) for managing CDI risks from clinical surfaces.

Keywords:
Clostridioides difficiledose–response modelinfectionquantitative microbial risk assessmentrisk

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Last Updated: Jun 3, 2026

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment
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A Protocol to Characterize the Morphological Changes of Clostridium difficile in Response to Antibiotic Treatment

Published on: May 25, 2017

Area of Science:

  • Microbiology
  • Risk Assessment
  • Infectious Diseases

Background:

  • Effective management of Clostridioides difficile infection (CDI) is hindered by the absence of a human dose-response model.
  • Existing challenges in risk assessment stem from insufficient human data for C. difficile.

Purpose of the Study:

  • To develop a novel murine-derived dose-response model for C. difficile that mirrors human CDI.
  • To apply this model within a quantitative microbial risk assessment (QMRA) framework to evaluate CDI risk from clinical surfaces.

Main Methods:

  • Evaluated animal dose-response datasets for C. difficile, selecting a mouse model of C. difficile-associated colitis.
  • Utilized maximum likelihood estimation in R to fit data to beta-Poisson and exponential models.
  • Assessed model fit using Akaike information criterion, Bayesian information criterion, likelihood tests, and sensitivity analysis.

Main Results:

  • The beta-Poisson model demonstrated the best fit (α = 0.56, N50 = 2871.56).
  • Estimated mean doses for 10% and 50% infection rates were 505 and 3994 CFU, respectively.
  • QMRA application indicated potential annual CDI risks: 33 cases per 100,000 healthcare workers from bed rails, 12 from keyboards, and <1 from door handles.

Conclusions:

  • The study successfully established a C. difficile dose-response relationship using a murine model.
  • This provides a foundation for future QMRA research on C. difficile.
  • Supports the development of context-specific risk assessments for CDI in healthcare settings.