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Determination of Multiple Dosing Parameters: Loading and Maintenance Doses01:25

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

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A loading dose is an essential pharmacological strategy to rapidly achieve the target plasma drug concentration necessary for an immediate therapeutic effect. This approach is especially critical for drugs characterized by slow absorption or extended half-lives, where delaying therapeutic plasma levels could compromise treatment outcomes. By administering a loading dose, clinicians ensure a prompt onset of drug action, even for agents with complex pharmacokinetic profiles.Achieving steady-state...
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Dosage Regimen Designs: Nomograms and Tabulations01:23

Dosage Regimen Designs: Nomograms and Tabulations

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Nomograms and tabulations are vital tools used by clinicians to design accurate and individualized dosage regimens. These instruments provide a straightforward method for adjusting dosages based on individual patient characteristics, including age, weight, and physiological condition. The foundation of a drug's nomogram is population pharmacokinetic data collected and analyzed using specific models. This data simplifies complex equations, presenting them diagrammatically or tabularly for easy...
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Dose Size and Dosing Frequency: Determination Methods01:21

Dose Size and Dosing Frequency: Determination Methods

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Determining the optimal dose size and dosing frequency in pharmacotherapy is crucial for achieving therapeutic effectiveness while minimizing adverse effects. This article explores the methodologies employed in determining these parameters, focusing on their significance and interplay to tailor dosing regimens.Dose Size: Dose size refers to the amount of a drug administered in a single dose. It is determined based on the drug's pharmacodynamics and pharmacokinetics properties and...
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Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
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Dosage Regimens: Partial Pharmacokinetic Parameters01:01

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...
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Uncertainty: Confidence Intervals00:54

Uncertainty: Confidence Intervals

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The confidence interval is the range of values around the mean that contains the true mean. It is expressed as a probability percentage. The interpretation of a 95% confidence interval, for instance, is that the statistician is 95% confident that the true mean falls within the interval. The upper and lower limits of this range are known as confidence limits. The confidence limits for the true mean are estimated from the sample's mean, the standard deviation, and the statistical factor...
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Related Experiment Video

Updated: Mar 28, 2026

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies
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Optimal radiotherapy dose schedules under parametric uncertainty.

Hamidreza Badri1, Yoichi Watanabe, Kevin Leder

  • 1Department of Industrial and Systems Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

Physics in Medicine and Biology
|December 19, 2015
PubMed
Summary

This study introduces a stochastic approach to radiation scheduling, accounting for patient variability to optimize treatment. This method ensures treatment effectiveness and safety by managing uncertainties in radiosensitivity and organ-at-risk sparing.

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Area of Science:

  • * Radiation Oncology
  • * Medical Physics
  • * Computational Biology

Background:

  • * Inter-patient variability in normal and tumor tissue radiosensitivity, and organ-at-risk (OAR) sparing factors, can significantly degrade radiotherapy efficacy or lead to OAR over-dosing.
  • * Conventional radiation scheduling models often do not account for these uncertainties, potentially compromising treatment outcomes.
  • * Optimizing radiation schedules requires robust methods that incorporate biological variability.

Purpose of the Study:

  • * To develop a stochastic radiation scheduling concept that integrates inter-patient variability into the optimization problem.
  • * To ensure treatment constraints are met with a specified probability and the objective function achieves a desired level.
  • * To compare optimal schedules under uncertainty with conventional schedules and analyze the impact of parameter uncertainty.

Main Methods:

  • * A probabilistic approach was employed, treating model parameters as random variables.
  • * Variable transformation was used to reduce the optimization problem's dimensionality.
  • * A branch and bound algorithm was implemented to find the global optimal solution.

Main Results:

  • * Optimal solutions were found to lie on the boundary of the feasible region.
  • * Stochastic schedules avoid extremal solutions (e.g., single large doses or prolonged treatment) to mitigate risks associated with parameter uncertainty.
  • * Numerical experiments in head and neck cancer demonstrated the impact of parameter uncertainty on optimal schedules and parameter sensitivity.

Conclusions:

  • * Stochastic radiation scheduling effectively incorporates inter-patient variability, enhancing treatment robustness.
  • * Accounting for uncertainty leads to non-extremal schedules, balancing efficacy and safety.
  • * The proposed method provides a framework for personalized radiation therapy planning by considering biological variability.