An in Vitro Study of Diamorphine Permeation Through Premature Human Neonatal Skin

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Abstract
The permeation kinetics of diamorphine through human premature neonatal cadaver skin over a range of gestational ages between 24 and 36 weeks was investigated using small diffusion cells. A strong inverse correlation was noted between the apparent permeability coefficient and the gestational age of the skin (P < 0.01; n = 26). The calculated apparent permeability coefficients decreased with gestational age from 6.0 × 10 −2 cm · hr−1 at 24 weeks' gestation to 5.2 × 10−6 cm · hr−1 at 36 weeks' gestation. The amount of diamorphine remaining bound within the skin at the end of the in vitro experiments did not change significantly with gestational age of the skin. Diamorphine was subject to degradation over the course of the in vitro experiments to produce significant amounts of 6-mono-acetylmorphine and evidence is presented to suggest that this was due to residual skin esterase activity. It is calculated that the steady-state flux rate of diamorphine through neonatal skin observed in these experiments would be sufficient to obtain a therapeutic plasma concentration of morphine assuming a 2-cm2 area for application and a delivery rate of 15 µg hr −1 kg−1. However, the prolonged half-life of morphine in the premature neonate would result in a delay of some hours before the attainment of this level.