P-glycoprotein in the developing human brain: A review of the effects of ontogeny on the safety of opioids in neonates

The human blood brain barrier is responsible for maintaining brain homeostasis and protecting against potentially toxic substances. The ATP-binding cassette drug efflux protein, P-glycoprotein (P-gp) is a key player in actively extruding a wide range of xenobiotics such as opioids from the brain. Because the blood brain barrier is structurally and functionally immature in neonates, opioids may have a greater penetration to the central nervous system. This may influence the efficacy and safety of opioids in the newborn. Understanding the extent of P-gp's expression in the brain in the embryo, fetus, and newborn will facilitate rational opioid use during pregnancy and the neonatal period. This review aims to summarize the current evidence that associates the ontogeny of P-gp and the susceptibility to opioid-induced adverse respiratory effects in neonates. To date, evidence suggests that the expression of P-gp in the human brain is low at birth, contributing to increased susceptibility.