Paediatric Fentanyl Population Pharmacokinetics: A Scoping Review of Published Models

Fentanyl is a highly lipophilic opioid widely used within paediatric peri-operative and intensive-care settings, yet dosing is commonly titrated empirically because of substantial pharmacokinetic variability across developmental stages and clinical contexts. Population pharmacokinetic (PopPK) models provide a quantitative framework to characterise variability, but these have not been systematically synthesised. This scoping review aimed to identify and summarise published paediatric PopPK models of fentanyl, to compare model structures and covariate effects.

We searched Embase and MEDLINE databases from database inception to 17 February 2026 for paediatric PopPK models of fentanyl. Two reviewers independently screened papers and extracted data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines.

Fourteen paediatric PopPK models of fentanyl were identified. Infants (64%, 9/14) and patient populations spanning multiple age groups (e.g., inclusion of infants and children) (64%, 9/14) were most frequently studied. Intravenous fentanyl was modelled in all studies. Two-compartment structures predominated (79%, 11/14). Body weight was the most consistently retained covariate (79%, 11/14), while maturation functions based on postnatal or postmenstrual age were frequently required in neonatal and infant cohorts (50%, 5/10). Other covariates (e.g., obesity, concomitant CYP3A modulators, and genetic factors) were variably explored and inconsistently retained.

Within the existing fentanyl literature, important evidence gaps remain, particularly beyond intravenous administration. Existing models highlight body weight and developmental maturation as principal determinants of clearance and distribution. Evidence remains limited to intravenous administration, with no model data of non-intravenous routes and under-representation of dynamic covariates and external validation. Addressing these gaps will support robust model-informed precision dosing of fentanyl in children.