■ INTRODUCTION
Propofol is frequently used for induction of anesthesia and procedural sedation, including off label use in (pre)term neonates. Despite its availability for almost 30 years, neonatal propofol pharmacokinetics remain poorly studied1. Propofol is only approved for clinical use in children 3 years of age or older2. Propofol is a lipophilic compound that undergoes hepatic metabolism via hydroxylation by cytochrome P450 (CYP) isoforms (CYP2B6 and CYP3A4) and glucuronidation by 5’-diphospho-glucuronosyltransferase 1A9 (UGT1A9)3,4. Differences in the abundance and activity of these enzymes between different age groups are reported in literature5. Therefore, age-dependency of size adjusted pharmacokinetic parameters (maturation) was reported earlier, and was anticipated in the current analysis. Enzyme maturation is largely complete at 2 years of age, but a prominent determinant of drug metabolism in neonates6,7. Maturation of propofol elimination clearance in neonates has been modeled based on postmenstrual age (PMA), the sum of gestational age (GA) and postnatal age (PNA), not always separately accounting for changes in body size/weight8. These simplifications may not be fully appropriate for preterm neonates. Age and weight correlate substantially in this population and may confound covariate effects9. In addition, pre and postnatal maturation are not expected to follow the same trajectory. A postmenstrual age of 38 weeks most likely reflects different maturation in a 8 weeks old neonate born after 30 weeks of gestation versus a full term neonate immediately after birth. Since currently available population pharmacokinetic models for propofol in neonates lack granularity in this regard, we expanded these models in order to optimally capturing size and maturation effects8,10,11.