Therapeutic Drug Monitoring in Neonates: What Makes them Unique?

Title:Therapeutic Drug Monitoring in Neonates: What Makes them Unique?

Volume: 23 Issue: 38

Author(s): P. Mian*, R.B. Flint, D. Tibboel, J.N. van den Anker, K. Allegaert and B.C.P. Koch

Affiliation:

• Intensive Care and Department of Pediatric Surgery, Erasmus University Medical Center - Sophia, Rotterdam,Netherlands

Keywords: Therapeutic drug monitoring, pharmacokinetics, PK/PD, neonate, endogenous substances, pharmacodynamics.

Abstract: Introduction: Therapeutic drug monitoring (TDM) refers to the interpretation of quantified drug concentrations in strategically timed samples of bodily fluids, with the aim to maximize therapeutic benefit, while minimizing toxicity. In essence, TDM criteria for neonates are similar to those for adults, but specific issues should be considered. This review focusses on the relevance of these specific issues: larger variability in pharmacokinetics (PK), and non-PK related factors, sampling opportunities, analytical techniques, therapeutic range.

Specific issues: Larger variability in PK, and non-PK related factors in neonates compared to adults result in a less clear relation between the administered dose and the concentration measured. Sophisticated dosing regimens derived from population PK-models can partly overcome this variability, thereby reducing the need for TDM. Dosing can be further individualized using Bayesian forecasting as a tool for TDM. Besides PK related factors, concentrations of endogenous substances (e.g. immunoglobulin A, plasma protein) in neonates differ from those in adults, which may complicate interpretation of measured drug concentrations. Blood sampling opportunities in neonates are limited by the small blood volume and the need to minimize painful procedures. Dried blood spot sampling may be less invasive. This method has been facilitated by more sensitive analytical techniques, such as chromatography followed by mass spectrometry. For the same reason, saliva is gaining attention as an alternative non-invasive bodily fluid. Lastly, reference values for therapeutic ranges of drugs in neonates are mostly adapted from adult studies, although pharmacodynamics may be quite different in neonates.

This review concludes with recommendations for future research on these specific issues.

Cite this article as:

Mian P.*, Flint R.B., Tibboel D., van den Anker J.N., Allegaert K. and Koch B.C.P., Therapeutic Drug Monitoring in Neonates: What Makes them Unique?, Current Pharmaceutical Design 2017; 23 (38) . https://dx.doi.org/10.2174/1381612823666170926143820

DOI https://dx.doi.org/10.2174/1381612823666170926143820	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286