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Related Concept Videos

Drug Dosing: Geriatric Patients01:15

Drug Dosing: Geriatric Patients

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Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...
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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: 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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Drug Dosing: Infants and Children01:29

Drug Dosing: Infants and Children

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Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
293
Rational Dosage Regimen: Maintenance Dose and Loading Dose01:24

Rational Dosage Regimen: Maintenance Dose and Loading Dose

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A rational dosage regimen considers a drug's pharmacokinetics, including its absorption, distribution, metabolism, and elimination from the body. By understanding these factors, the appropriate dosage can be determined, and the dosing schedule can be designed to achieve and maintain the desired therapeutic effect while minimizing adverse effects.
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Dose-Response Relationship: Overview01:03

Dose-Response Relationship: Overview

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Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
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Related Experiment Video

Updated: Jan 31, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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A unified anti-mutant dosing strategy.

Xilin Zhao1, Karl Drlica

  • 1Public Health Research Institute, New Jersey Medical School, UMDNJ, 225 Warren Street, Newark, NJ 07103, USA.

The Journal of Antimicrobial Chemotherapy
|June 12, 2008
PubMed
Summary

Minimizing antimicrobial resistance requires optimized dosing. Current strategies are flawed; combining mutant prevention concentration (MPC) with pharmacokinetic/pharmacodynamic (PK/PD) thresholds offers a promising approach to restrict resistant bacteria.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Antimicrobial resistance is a growing global health concern.
  • Current antimicrobial dosing strategies have limitations in preventing resistance.
  • Existing methods fail to adequately address pre-existing or therapy-induced resistant mutant subpopulations.

Purpose of the Study:

  • To evaluate the shortcomings of current antimicrobial dosing strategies.
  • To propose and explore the utility of mutant prevention concentration (MPC)-based pharmacokinetic/pharmacodynamic (PK/PD) thresholds.
  • To demonstrate how MPC-based thresholds can restrict resistant subpopulation enrichment and amplification.

Main Methods:

  • Analysis of existing antimicrobial dosing strategies (killing susceptible cells, maintaining drug concentration above mutant prevention concentration (MPC), dosage escalation modeling).

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  • Comparison of Minimum Inhibitory Concentration (MIC) and MPC values across multiple pathogen isolates.
  • Conceptualization of MPC-based PK/PD thresholds (e.g., AUC(24)/MPC, t > MPC).

    • Main Results:

    • Focusing solely on susceptible cell killing overlooks resistant subpopulations.
    • Maintaining concentrations above MPC may be excessively stringent.
    • Dosage escalation modeling relies on indirect susceptibility estimates, differing from direct MPC measurements, which are critical as MIC and MPC can be discordant.

    Conclusions:

    • Combining antimicrobial dosing strategies with MPC-based PK/PD thresholds is essential for restricting resistant subpopulation growth.
    • Development of comprehensive databases with MPC values for diverse isolates is necessary for effective dosing regimen modeling.
    • MPC-based dosing represents a critical advancement in antimicrobial stewardship to combat resistance.