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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
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Model-informed precision dosing in vancomycin treatment.

Sukyong Yoon1,2, Jinju Guk1,2, Sang-Guk Lee3

  • 1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Frontiers in Pharmacology
|October 25, 2023
PubMed
Summary
This summary is machine-generated.

This study developed a precision dosing model for vancomycin (an antibiotic) to optimize treatment and reduce toxicity. The model helps determine ideal dosages and durations, ensuring effectiveness while minimizing side effects like kidney damage.

Keywords:
C-reactive proteinNONMEMR shinymodel-informed precision dosingoptimal dosepharmacodynamicpharmacokineticvancomycin

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Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Pharmacometrics

Background:

  • Vancomycin is a critical antibiotic but associated with ototoxicity and nephrotoxicity.
  • Concentration-dependent toxicity and overtreatment necessitate optimized dosing strategies.

Purpose of the Study:

  • To develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for vancomycin.
  • To establish a model-informed precision dosing scheme for optimal dosage and treatment duration.
  • To minimize vancomycin-induced toxicity.

Main Methods:

  • Analysis of electronic medical records from 542 patients (including 40 children) using NONMEM software.
  • Development of a two-compartment PK model with allometric scaling for vancomycin concentrations.
  • Modeling of C-reactive protein (CRP) plasma concentrations using transit compartments for PD analysis.

Main Results:

  • Vancomycin clearance is influenced by creatinine, BUN, diabetes, renal disease history, and sex; volume of distribution increases with age.
  • CRP levels decreased with pneumonia and were modeled effectively.
  • Simulations showed optimal dosing maintained therapeutic concentrations with potentially lower doses, and higher doses accelerated CRP reduction.

Conclusions:

  • A population PK/PD model can guide precision dosing for vancomycin.
  • The model facilitates the design of optimal vancomycin treatment regimens to reduce toxicity.
  • An R Shiny application enables efficient visualization for designing personalized treatment schemes.