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Pharmacodynamic Models: Overview

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Pharmacodynamic (PD) responses describe the interaction between a drug and its biological target, culminating in a physiological effect. These responses can be classified into different types: continuous variables, such as blood glucose levels; categorical outcomes, like survival rates; and time-to-event metrics, such as disease progression. Understanding and modeling PD responses are critical for optimizing drug efficacy and safety.PD models describe the relationship between drug concentration...

Dosage Regimens: Partial Pharmacokinetic Parameters

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It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...

Estimation of k and VD of Aminoglycosides

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Aminoglycosides are a class of antibiotics used to treat various bacterial infections. Clinicians must determine the elimination rate constant (k) and volume of distribution (VD) to optimize therapeutic efficacy and minimize toxicity. The k value represents the rate at which the drug is removed from the body, and the VD reflects the degree to which the drug distributes into body tissues. Accurately estimating these parameters allows healthcare professionals to tailor drug dosing to individual...

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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...

Noncompartmental Analysis: Miscellaneous Pharmacokinetic Parameters

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Related Experiment Video

Updated: Jun 22, 2026

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii

Published on: January 2, 2017

Antimicrobial breakpoint estimation accounting for variability in pharmacokinetics.

Goue Denis Gohore Bi¹, Jun Li, Fahima Nekka

¹Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada. gd.gohore.bi@umontreal.ca

Theoretical Biology & Medical Modelling

|June 30, 2009

Summary

This study introduces a novel weighted area under the curve (AUC) method to improve pharmacokinetic/pharmacodynamic (PK/PD) analysis for antibiotic dosing. This approach enhances treatment efficacy prediction by accounting for variable PK profiles, offering a more robust link than traditional methods.

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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

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Last Updated: Jun 22, 2026

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii

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Published on: January 2, 2017

Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method

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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

Area of Science:

Pharmacology
Microbiology
Computational Biology

Background:

Pharmacokinetic/pharmacodynamic (PK/PD) indices are crucial for assessing antibiotic dosing regimen efficacy.
Traditional PK/PD methods using single values like AUC or Cmax can be biased by high variability.
Existing methods often fail to fully capture in vivo conditions due to PK variability.

Purpose of the Study:

To develop an adjusted breakpoint estimation method for variable PK profiles.
To evaluate treatment efficacy by accounting for PK variability.
To provide a more accurate PK/PD link for antibiotic efficacy assessment.

Main Methods:

Proposed a generalization of AUC methods by incorporating an "efficiency" concept for PK profiles.
Developed methods for both concentration- and time-dependent antibiotics.
Utilized drug models and in silico approaches to characterize PK profile efficiency under in vivo conditions.

Main Results:

Introduced a weighted AUC approach for PK/PD analysis.
Demonstrated theoretical basis for characterizing PK profile efficiency.
Assessed the impact of variable drug intake on PK profiles and breakpoint estimation.

Conclusions:

The weighted AUC approach provides a stronger PK/PD link compared to traditional methods.
The study highlights issues regarding therapeutic outcome indices and antibiotic resistance.
Offers a more nuanced understanding of antibiotic efficacy in the presence of PK variability.