scholarly journals PBPK Modeling and Simulation and Therapeutic Drug Monitoring: Possible Ways for Antibiotic Dose Adjustment

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 2087
Author(s):  
Abigail Ferreira ◽  
Rui Lapa ◽  
Nuno Vale
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Modeling And Simulation ◽  
Clinical Outcomes ◽  
Drug Monitoring ◽  
New Drugs ◽  
Pbpk Modeling ◽  
Therapeutic Drug ◽  
Human Pharmacokinetics ◽  
Bacterial Strains ◽  
Post Market

Pharmacokinetics (PK) is a branch of pharmacology present and of vital importance for the research and development (R&D) of new drugs, post-market monitoring, and continued optimizations in clinical contexts. Ultimately, pharmacokinetics can contribute to improving patients’ clinical outcomes, helping enhance the efficacy of treatments, and reducing possible adverse side effects while also contributing to precision medicine. This article discusses the methods used to predict and study human pharmacokinetics and their evolution to the current physiologically based pharmacokinetic (PBPK) modeling and simulation methods. The importance of therapeutic drug monitoring (TDM) and PBPK as valuable tools for Model-Informed Precision Dosing (MIPD) are highlighted, with particular emphasis on antibiotic therapy since dosage adjustment of antibiotics can be vital to ensure successful clinical outcomes and to prevent the spread of resistant bacterial strains.

scholarly journals Impact of Triazole Therapeutic Drug Monitoring Availability and Timing

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Erin K. McCreary ◽  
Meg Bayless ◽  
Ahn P. Van ◽  
Alexander J. Lepak ◽  
Donald A. Wiebe ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Outcomes ◽  
Antifungal Therapy ◽  
Drug Concentration ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Reference Laboratory ◽  
Serum Concentrations ◽  
Concentration Result ◽  
The Impact

ABSTRACT Therapeutic drug monitoring (TDM) is an established strategy to optimize antifungal therapy with certain triazoles. While established relationships exist between concentration and safety or efficacy, the impact of TDM timing on outcomes is unknown. We report clinical outcomes, including antifungal exposure and mortality, in patients receiving institutional versus reference laboratory TDM. The availability of in-house triazole assays reduced the time to drug concentration result (12 versus 68 h; P < 0.001) and time to achieve therapeutic serum concentrations (10 versus 31 days; P < 0.001). Subtherapeutic concentrations were associated with higher patient mortality (32% versus 13.3%; P = 0.036).

scholarly journals Therapeutic Drug Monitoring and Clinical Outcomes in Immune Mediated Diseases

2016 ◽  
Vol 22 (10) ◽  
pp. 2527-2537 ◽  
Author(s):  
Dario Sorrentino ◽  
Vu Nguyen ◽  
Carl Henderson ◽  
Adegabenga Bankole
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Outcomes ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Immune Mediated

scholarly journals Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonja E. Zapke ◽  
Stefan Willmann ◽  
Scott-Oliver Grebe ◽  
Kristin Menke ◽  
Petra A. Thürmann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Pbpk Model ◽  
Clinical Population ◽  
Pbpk Modeling ◽  
Additional Patient ◽  
Therapeutic Drug ◽  
Model Parameters ◽  
Drug Levels ◽  
Trough Levels

This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = −379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model’s performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.

scholarly journals Is There a Role for the Therapeutic Drug Monitoring of Colistin? An Overview

2020 ◽  
Vol 13 (3) ◽  
pp. 42
Author(s):  
Maria-Paula Avila ◽  
Tatiana Pacheco ◽  
Sara Arias ◽  
Rosa-Helena Bustos ◽  
Julio-Cesar Garcia ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Clinical Outcomes ◽  
Drug Monitoring ◽  
Dose Adjustment ◽  
Therapeutic Drug ◽  
Gram Negative ◽  
Electronic Search ◽  
Multiresistant Bacteria

Colistin is used as a last-line antibiotic for the treatment of Gram-negative multiresistant bacteria. Due to its high nephrotoxicity, Therapeutic Drug Monitoring (TDM) is recommended for dose adjustment. We aimed to evaluate the available evidence of TDM in patients given colistin to treat Gram-negative infections. In this paper, we offer an overview, using an electronic search of the literature (published up to June 2019, without language restrictions) that compares the clinical outcomes and measurements of colistin TDM. Ultimately, the Therapeutic Drug Monitoring (TDM) of colistin in Plasma could prevent nephrotoxicity risk.

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