Applied pharmacokinetics to improve pharmacotherapy in neonatal and paediatric intensive care units: focus on correct dose selection

Abstract

Drug dosing and exposure throughout childhood are constantly affected by maturational changes like weight, age or body surface area. In neonatal and paediatric intensive care units (NICU and PICU, respectively), drug dosing and exposure are further impacted by non-maturational changes. These changes are related to factors such as sepsis, cardiac failure, acute kidney injury, extracorporeal circuits or drug-drug interactions (DDIs) resulting from polypharmacy.This potentially complex situation may alter drug pharmacokinetics to result in greater-than-usual intrapatient and interpatient drug exposure variability. These effects may call for individual dosage adjustments. Dosage adjustments may apply to both loading doses or maintenance doses, which should be used as appropriate, depending on the specific characteristics of a given drug. Phenobarbital and vancomycin dosing are hereby used as illustrations.To optimise dose selection in NICU/PICU settings, we suggest to consider therapeutic drug monitoring integrated in model-informed precision dosing, and to familiarise oneself with existing paediatric drug formularies as well as DDI databases/search engines. Paediatric clinical pharmacologists and pharmacists can hereby guide clinicians with no prior experience on how to properly apply these data sources to day-to-day practice in individual patients or specific subpopulations of NICU or PICU patients.