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Related Concept Videos

Drug Dosing: Obese Patients01:21

Drug Dosing: Obese Patients

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In the United States, obesity is a prominent concern. It is linked to heightened mortality rates due to increased occurrences of conditions such as hypertension, atherosclerosis, coronary artery disease, and diabetes compared to nonobese individuals. A patient is classified as obese if their actual body weight surpasses the ideal or desirable body weight by 20%, based on Metropolitan Life Insurance Company data. Ideal body weights consider average weights and heights for males and females...
217
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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Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

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Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
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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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Pharmacokinetics in Obese Patients: Drug Absorption and Distribution01:25

Pharmacokinetics in Obese Patients: Drug Absorption and Distribution

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Obesity significantly alters the pharmacokinetic processes of drug absorption and distribution, presenting unique challenges in medical treatment. The increased fat tissue and decreased lean muscle in obese individuals can significantly affect how drugs are absorbed into the body and distributed across different tissues. This alteration can lead to variances in the effectiveness and safety of medications, necessitating adjustments in dosing or drug selection for obese patients.One notable...
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Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

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Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
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Related Experiment Video

Updated: Jan 13, 2026

Self-Administration of Drugs in Mouse Models of Feeding and Obesity
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Virtual Twin-PBPK Modelling: A Step Toward Precision Dosing in Patients with Obesity.

Haribhau Kangne1, Nihan Izat1, Gong Chen1

  • 1Division of Pharmacy and Optometry, School of Health Sciences, Centre for Applied Pharmacokinetic Research, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.

The AAPS Journal
|January 8, 2026
PubMed
Summary

Virtual-twin physiologically-based pharmacokinetic (VT-PBPK) models accurately predict drug levels in obesity. This approach shows promise for optimizing individual drug doses in obese populations.

Keywords:
PBPKdigoxinmidazolamobesityvirtual twins

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Obesity and Precision Dosing
  • Computational Modeling in Medicine

Background:

  • Obesity significantly impacts drug pharmacokinetics (PK), leading to considerable inter-individual variability.
  • The virtual-twin concept offers a promising avenue for model-informed precision dosing in specific patient populations.
  • Physiologically-based pharmacokinetic (PBPK) models are increasingly utilized to understand and predict drug behavior.

Purpose of the Study:

  • To develop and apply virtual-twin PBPK (VT-PBPK) models to predict midazolam and digoxin PK in patients with obesity and severe obesity.
  • To assess the accuracy of VT-PBPK models through stepwise individualization using demographic and biomarker data.
  • To evaluate the potential of VT-PBPK for optimizing drug dosing in the obese population.

Main Methods:

  • Development of VT-PBPK models incorporating demographic data, lean liver volume, serum creatinine, albumin, and hepatic enzyme/transporter abundance (CYP3A4/5, UGT1A4, P-gp) from liver biopsies.
  • Stepwise individualization of models to improve prediction accuracy for midazolam and digoxin.
  • Validation of model predictions against observed PK parameters (AUC, Cmax) in patients with obesity (n=15) and severe obesity (n=22).

Main Results:

  • The final VT-PBPK models predicted midazolam AUC0-inf,iv within 2-fold for 86% of individuals (GMFE=1.5), with 36% within 0.8-1.25 fold.
  • For digoxin, 97% of Cmax and AUC0-24 values were predicted within 2-fold (GMFE=1.25), with 59% within the 0.8-1.25 fold range.
  • Prediction accuracy for digoxin was notably higher in patients with severe obesity.

Conclusions:

  • VT-PBPK modeling represents a novel and effective approach for predicting drug pharmacokinetics in patients with obesity.
  • The study demonstrates the potential of VT-PBPK to support individualized dose optimization for midazolam, digoxin, and potentially other CYP3A and P-gp substrates.
  • This methodology offers a pathway towards more precise and effective drug therapy in the growing obese population.