Therapeutic Drug Monitoring (TDM) is defined as the measurement of drug plasma concentrations at a specific time in a dosing interval. This determination, following appropriate medical interpretation and according to the drug pharmacokinetic/pharmacodynamic (PK/PD) properties, will directly lead to a dose optimization. However, finding the optimal dosing in order to guarantee a therapeutic exposure to treated patients remains complicated. In fact, individual variability including age, genetic heritage and disease conditions are a limiting factor to the achievement of successful therapeutic outcomes, making the paradigm “one-dose-fits-all” often unfeasible. This aspect is particularly evident in children and neonates where physiological changes, associated with growth and maturation, dramatically influence drug PK properties. Similarly, pediatric patients subjected to medical procedures, including dialysis or Extra-Corporeal Membrane Oxygenation (ECMO), require special dose considerations since these procedures significantly affect PK parameters. Therefore, TDM represents an useful tool that allows a more tailored drug administration and, therefore, the individualization of therapy to avoid risks of therapeutic failures or drug toxicity.
Utility of TDM is often underestimated or exclusively applied to molecules where monitoring of therapeutic drug concentration is mandatory due to their low safety profile. In some cases, although benefits of TDM are well known and recognized by clinicians, this knowledge seems to be only theoretical and its introduction into clinical practice remains far away from the application. Additionally, TDM should rely on analytical methods such as high performance liquid chromatography (HPLC) or liquid chromatography associated to mass spectrometry (LC-MS/MS) characterized by fast detection, accuracy and data robustness. These equipment are not always available in every analytical laboratory and this aspect contributes to make TDM often unfeasible. Another issue that often accompanies TDM application to pediatric patients is the blood sampling. In fact, a limit in performing analyses in neonates and children is represented by the availability of low sampling volumes that make the analytical procedures not always applicable. In order to overcome this last issue, several microsampling methods have been proposed including volumetric absorptive microsampling (VAMS) and dried blood spots (DBS). However, so far evidences showing the analytical validation of these methods for conducting PK studies or their applicability to different drug classes are still limited.
This Research Topic aims to collect articles showing the application of TDM to the routine clinical practice in pediatric patients. In particular, themes that the editors would like to see addressed in this article collection are the following:
• TDM as main tool for conducing PK studies on neonates, infants, children and adolescents.
• Model-based therapy individualization using TDM approach in pediatric patients.
• Bioanalytical validation of microsampling techniques applied to PK studies or TDM during the routine clinical practice.
• Case-reports highlighting the importance of performing TDM in order to avoid risks of therapeutic failures or adverse drug reactions (ADRs) in pediatric patients.
• Current literature reporting the “state-of-the-art” of TDM applied to the pediatric pharmacology.
We welcome Original Research, Brief Research Reports, Reviews, and Study Protocol article types.
Therapeutic Drug Monitoring (TDM) is defined as the measurement of drug plasma concentrations at a specific time in a dosing interval. This determination, following appropriate medical interpretation and according to the drug pharmacokinetic/pharmacodynamic (PK/PD) properties, will directly lead to a dose optimization. However, finding the optimal dosing in order to guarantee a therapeutic exposure to treated patients remains complicated. In fact, individual variability including age, genetic heritage and disease conditions are a limiting factor to the achievement of successful therapeutic outcomes, making the paradigm “one-dose-fits-all” often unfeasible. This aspect is particularly evident in children and neonates where physiological changes, associated with growth and maturation, dramatically influence drug PK properties. Similarly, pediatric patients subjected to medical procedures, including dialysis or Extra-Corporeal Membrane Oxygenation (ECMO), require special dose considerations since these procedures significantly affect PK parameters. Therefore, TDM represents an useful tool that allows a more tailored drug administration and, therefore, the individualization of therapy to avoid risks of therapeutic failures or drug toxicity.
Utility of TDM is often underestimated or exclusively applied to molecules where monitoring of therapeutic drug concentration is mandatory due to their low safety profile. In some cases, although benefits of TDM are well known and recognized by clinicians, this knowledge seems to be only theoretical and its introduction into clinical practice remains far away from the application. Additionally, TDM should rely on analytical methods such as high performance liquid chromatography (HPLC) or liquid chromatography associated to mass spectrometry (LC-MS/MS) characterized by fast detection, accuracy and data robustness. These equipment are not always available in every analytical laboratory and this aspect contributes to make TDM often unfeasible. Another issue that often accompanies TDM application to pediatric patients is the blood sampling. In fact, a limit in performing analyses in neonates and children is represented by the availability of low sampling volumes that make the analytical procedures not always applicable. In order to overcome this last issue, several microsampling methods have been proposed including volumetric absorptive microsampling (VAMS) and dried blood spots (DBS). However, so far evidences showing the analytical validation of these methods for conducting PK studies or their applicability to different drug classes are still limited.
This Research Topic aims to collect articles showing the application of TDM to the routine clinical practice in pediatric patients. In particular, themes that the editors would like to see addressed in this article collection are the following:
• TDM as main tool for conducing PK studies on neonates, infants, children and adolescents.
• Model-based therapy individualization using TDM approach in pediatric patients.
• Bioanalytical validation of microsampling techniques applied to PK studies or TDM during the routine clinical practice.
• Case-reports highlighting the importance of performing TDM in order to avoid risks of therapeutic failures or adverse drug reactions (ADRs) in pediatric patients.
• Current literature reporting the “state-of-the-art” of TDM applied to the pediatric pharmacology.
We welcome Original Research, Brief Research Reports, Reviews, and Study Protocol article types.