Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents

Asín-Prieto, Eduardo; Rodríguez-Gascón, Alicia; Isla, Arantxazu

doi:10.1016/j.jiac.2015.02.001

Cited by 186 publications

(185 citation statements)

References 104 publications

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“…Three types of PK‐PD indices were commonly considered for evaluating the efficacy of antimicrobial drugs: T > MIC (duration of the drug concentration remains above the MIC), C max /MIC (the ratio of C max to MIC) and AUC/MIC (the ratio of AUC to MIC). Selection of the best PK‐PD index depends on the killing nature of the antimicrobials (AliAbadi & Lees, ; Asín‐Prieto, Rodríguez‐Gascón, & Isla, ; Levison, ; Mckellar, Sanchez Bruni, & Jones, ; Toutain, Del Castillo, & Bousquet‐Mélou, ). In general, the most suitable PK‐PD index for time‐dependent bacteriostatic drugs without prolonged post‐antibiotic effect (including FF) is T > MIC in which free drug concentration (the fraction that not binds to plasma/serum proteins) should be greater than the target MIC over at least 50%–80% of the dosing interval (Levison, ; Toutain et al, ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels

Rairat

Hsieh

Thongpiam

et al. 2019

Journal of Fish Diseases

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Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature‐dependent PK and the pathogen‐dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg−1 day−1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cmin(ss) while at 28 and 32°C underestimation of the Cmin(ss) in a dose‐dependent manner was observed and likely due to the occurrence of non‐linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK‐PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non‐linearity of FF in tilapia warrant further study.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels

Rairat

Hsieh

Thongpiam

et al. 2019

Journal of Fish Diseases

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“…In addition, this trial had not assessed SXT resistance. Methods including pharmacokinetic/pharmacodynamic (PK/PD) analyses to determine PK/PD indices to optimize efficacy and avoid emerging resistance are needed for SXT (14, 15). Furthermore, it is known that SXT has a shorter half-life in children (16).…”

Section: What Did We Learn?mentioning

confidence: 99%

Community-Based Prescribing for Impetigo in Remote Australia: An Opportunity for Antimicrobial Stewardship

Oliver

Cush

Ward

2017

Front. Public Health

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BackgroundTo support antibiotic prescribing for both hospital and community-based health professionals working in remote North Western Australia, a multidisciplinary Antimicrobial Stewardship (AMS) Committee was established in 2013. This Committee is usually focused on hospital-based prescribing. A troubling increase in sulfamethoxazole/trimethoprim resistance in Staphylococcus aureus antibiograms from 9 to 18% over 1 year prompted a shift in gaze to community prescribing.What we didFinding a paucity of relevant research, we first investigated contextual factors influencing local prescribing. We also designed a systematic survey of experts with experience relevant to our setting using a structured response survey (12 questions) to better understand specific AMS risks. Using these findings, recommendations were formulated for the AMS Committee.What we learnedPrescribing recommendations in a regional Skin Infections Protocol had previously been altered in December 2014. From 15 experts, we received 9 comprehensive responses (60%) about AMS risks in community prescribing. If feasible, prescribing audits also would have been valuable. Ten recommendations regarding specific antibiotic recommendations were submitted to the AMS Committee.Strengthening AMS in remote settingsAs AMS Committees in Australia usually focus on hospital-based prescribing, novel methods such as external expert opinion could inform deliberations about community-based prescribing. Our approach meant that this AMS Committee was able to intervene in the 2017 organizational review of the regional Skin Infections Protocol used by prescribers likely unaware of AMS risks. This experience demonstrates the value of incorporating AMS principles in community-based prescribing in context of a remote setting.

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“…Several studies have shown how PKPD models leverage the link between dose, exposure, and response (Asin-Prieto et al, 2015; Girard et al, 2005; Nielsen et al, 2011). Integrated PKPD models aim to predict the response associated with a drug “at any time, after any dose, administered by any route”.…”

Section: Pharmacodynamic Modelsmentioning

confidence: 99%

On the analysis of complex biological supply chains: From process systems engineering to quantitative systems pharmacology

Rao

Scherholz

Hartmanshenn

et al. 2017

Computers & Chemical Engineering

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The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

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Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents

Cited by 186 publications

References 104 publications

Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels

Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels

Community-Based Prescribing for Impetigo in Remote Australia: An Opportunity for Antimicrobial Stewardship

On the analysis of complex biological supply chains: From process systems engineering to quantitative systems pharmacology

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