Naloxone protein binding in adult and foetal plasma.

Binding of naloxone hydrochloride was determined at 37 degrees C, by equilibrium dialysis against 0.067 M phosphate buffer, pH 7.4, in plasma obtained from 18 healthy adults, and 18 samples of umbilical cord venous (foetal) plasma. The percentage free fraction (% free) in plasma was independent of naloxone concentration (9 ng/ml to 2.5 micrograms/ml). Percent free naloxone in adult (means = 54.0) was lower (p less than 0.01) than in foetal (means = 61.5) plasma. In buffered solutions of purified HSA, %free naloxone (means = 68.7) was independent of HSA concentration over the range 3.0 g/dl to 5.5 g/dl. Adult plasma concentrations of alpha 1-acid glycoprotein (alpha 1-AGP) and beta-lipoprotein were higher (p less than 0.01) than foetal concentrations. Furthermore %free naloxone in foetal plasma decreased with the in-vitro addition of purified alpha 1-AGP. It is suggested that qualitative differences in adult and foetal albumin and quantitative differences in plasma levels of alpha 1-AGP and perhaps beta-lipoprotein are responsible for naloxone plasma binding differences between adults and the newborn.