Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Background: Major differences in physiology, and consequently pharmacology, exist between neonatal and adult populations. Additionally, most pharmacokinetic (PK) and -dynamic (PD) data are based on total drug concentrations, instead of the pharmacologically active unbound drug. Objectives: Our aim was to review current knowledge on in vivo drug-protein binding in different albumin bound drugs. Methods: We conducted a review, searching the electronic databases MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science. The inclusion criteria were based on three main concepts: 1) findings in neonates, defined as children up to 28 days old, 2) on albumin-bound compounds and 3) based on in vivo observations. Our main parameter of interest was unbound drug fraction (Fu, in %) and its covariates. Results: We identified 9 studies on 7 different compounds (bupivacaine, cefazolin, cefoperazone, flucloxacillin, phenytoin, phenobarbital and vancomycin). Neonatal drug Fu proved to be higher in neonates compared to older populations. Multiple covariates were significant predictors for neonatal Fu: albuminemia, total drug concentrations, maturation-related covariates, bilirubinemia, kidney function, free fatty acid concentrations and co-administration of other highly albumin-bound drugs. It is important to note that unbound drug fractions and concentrations were considered superior over total drug concentrations for optimal PK/PD modelling. Conclusion: We conclude that integration of in vivo neonatal parameters of drug-protein binding could help elaborate more sophisticated modelling on optimizing neonatal drug exposure and dosing regimens.