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Antibiotics
Special Issues
PK/PD Models for Optimizing Antibiotic Use and Avoiding Drug-Drug Interaction
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PK/PD Models for Optimizing Antibiotic Use and Avoiding Drug-Drug Interaction

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics of Drugs".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 5421

Special Issue Editors

Dr. Nahed El-Najjar

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon
Interests: pharmacology; toxicology and pharmaceutics; drug-drug interaction; personalized medicine; repurposed drugs
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Takahisa Yano

E-Mail Website
Guest Editor
Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo 693-8501, Japan
Interests: vancomycin; antibiotics; infection control; population pharmacokinetic analysis; proper use of antibiotics; drug-resistant bacteria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Optimizing antibiotic use is crucial in pharmacology as it allows for improving antimicrobial therapy while minimizing the development of resistance. Pharmacokinetic/pharmacodynamic (PK/PD) models are pivotal in understanding the relationship between drug exposure and desired therapeutic outcomes. By integrating pharmacokinetic parameters with pharmacodynamic endpoints, these models provide valuable insights into the dosing regimens and drug combinations that maximize antimicrobial efficacy. In addition, they can be essential for avoiding unwanted effects resulting from drug-drug interactions.

This Special Issue explores the various applications of PK/PD models in antibiotic optimization, showcasing the latest research findings, methodological advancements, and practical implications and highlighting potential interactions resulting from the simultaneous presence of antimicrobial therapy with other medications. Incorporating pharmacokinetic parameters (how drugs move within the body) and pharmacodynamic effects (how drugs interact with pathogens and other drugs) provides unique insights into antimicrobial dosing regimens, treatment strategies, and the development of new antibiotics. By delving into these areas, we hope to enhance our understanding of the underlying mechanisms driving antibiotic efficacy and resistance, ultimately informing clinical decision-making and improving patient outcomes.

Dr. Nahed El-Najjar
Dr. Takahisa Yano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pharmacokinetics
  • pharmacodynamics
  • clinical outcome
  • antimicrobial resistance
  • antibiotic use
  • drug-drug interaction

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Published Papers (3 papers)

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Research

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20 pages, 3945 KiB  
Article
Application of Physiologically Based Pharmacokinetic Model to Delineate the Impact of Aging and Renal Impairment on Ceftazidime Clearance
by Khaled Abduljalil, Iain Gardner and Masoud Jamei
Antibiotics 2024, 13(9), 862; https://doi.org/10.3390/antibiotics13090862 - 9 Sep 2024
Viewed by 1160
Abstract
The impact of physiological changes during aging on drug disposition has not always been thoroughly assessed in clinical studies. This has left an open question such as how and to what extent patho- and physiological changes in renal function can affect pharmacokinetics in [...] Read more.
The impact of physiological changes during aging on drug disposition has not always been thoroughly assessed in clinical studies. This has left an open question such as how and to what extent patho- and physiological changes in renal function can affect pharmacokinetics in the geriatric population. The objective of this work was to use a physiologically based pharmacokinetic (PBPK) model to quantify the impact of aging and renal impairment (RI) separately and together on ceftazidime pharmacokinetics (PK). The predicted plasma concentrations and PK parameters from the PBPK model were compared to the observed data in individuals of different ages with or without RI (16 independent studies were investigated in this analysis). Apart from clearance in one study, the predicted ceftazidime PK parameters of young adults, elderly, and in individuals with different levels of renal function were within 2-fold of the observed data, and the observed concentrations fell within the 5th–95th prediction interval from the PBPK model simulations. The PBPK model predicted a 1.2-, 1.5-, and 1.8-fold increase in the plasma exposure (AUC) ratio in individuals aged 40, 60, and 70 years old, respectively, with normal renal function for their age compared to 20-year-old individuals with normal renal function. The impact of RI on ceftazidime was predicted to be less marked in older individuals (a 1.04-, 1.43-, and 2.55-fold change in mild, moderate, or severe RI compared to a healthy age-matched control) than in younger individuals (where a 1.47-, 2.03-, and 3.50-fold increase was predicted in mild, moderate, or severe RI compared to a healthy age-matched control). Utilization of the applied population-based PBPK approach allows delineation of the effects of age from renal disease and can better inform future study design and dosing recommendations in clinical study of elderly patients depending on their age and renal function. Full article
(This article belongs to the Special Issue PK/PD Models for Optimizing Antibiotic Use and Avoiding Drug-Drug Interaction)
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14 pages, 1313 KiB  
Article
Precision Dosing of Meropenem in Adults with Normal Renal Function: Insights from a Population Pharmacokinetic and Monte Carlo Simulation Study
by Yong Kyun Kim, Gaeun Kang, Dae Young Zang and Dong Hwan Lee
Antibiotics 2024, 13(9), 849; https://doi.org/10.3390/antibiotics13090849 - 5 Sep 2024
Cited by 1 | Viewed by 1677
Abstract
This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect [...] Read more.
This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free (f) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions (fT>MIC). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40%fT>MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100%fT>MIC or a 90%PTA for 100%fT>4MIC, higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets. Full article
(This article belongs to the Special Issue PK/PD Models for Optimizing Antibiotic Use and Avoiding Drug-Drug Interaction)
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Review

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18 pages, 1214 KiB  
Review
PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance
by Tetsushu Onita, Noriyuki Ishihara and Takahisa Yano
Antibiotics 2025, 14(1), 92; https://doi.org/10.3390/antibiotics14010092 - 14 Jan 2025
Viewed by 1986
Abstract
Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, [...] Read more.
Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, focusing on three key aspects. First, we discuss the importance of drug concentration management for enhancing efficacy while preventing toxicity, considering various patient populations, including pediatric and elderly patients with their unique physiological characteristics. Second, we analyze different PK modeling approaches: the classic top-down approach exemplified by population PK analysis, the bottom-up approach represented by physiologically based PK modeling, and hybrid models combining both approaches for enhanced predictive performance. Third, we explore clinical applications, including nomogram-based dosing strategies, Bayesian estimation, and emerging artificial intelligence applications, for real-time dose optimization. Critical challenges in implementing PK/PD simulation are addressed, particularly the selection of appropriate PK models, the optimization of PK/PD indices, and considerations concerning antimicrobial concentrations at infection sites. Understanding these principles and challenges is crucial for optimizing antimicrobial therapy and combating AMR through improved dosing strategies. Full article
(This article belongs to the Special Issue PK/PD Models for Optimizing Antibiotic Use and Avoiding Drug-Drug Interaction)
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