Disentangling PK-PD in neonates

A commentary on the paper by Allegaert et al Neonatal analgesia is a humane consideration, and paracetamol offers a reasonable alternative for mild to moderate pain. The investigation of propacetamol, an intravenous prodrug of paracetamol (acetaminophen), in premature neonates after intravenous administration has received scant attention. We might expect propacetamol to offer advantages clinically because a plasma target concentration can be rapidly attained and variability due to absorption kinetics and relative bioavailability is reduced. In addition, an intravenous drug offers a cleaner pharmacokinetic study that can further our knowledge of paracetamol pharmacokinetics in premature and term neonates.1–5 Allegaert et al are to be congratulated for investigating propacetamol use in premature neonates. Neonatal pharmacokinetic studies are fraught with pitfalls. Clearance often increases rapidly after birth (postnatal age) no matter what the gestational age at birth. This study gets around this …