IN-VITRO PERCUTANEOUS-ABSORPTION EVALUATION OF PHENOBARBITAL THROUGH HAIRLESS MOUSE, ADULT AND PREMATURE HUMAN SKIN

In vitro phenobarbital flux through newborn (preterm and full-term) in fant, hairless mouse and adult human skin was determined using both Fr anz cells and flow-through diffusion cells. The phenobarbital flux val ue through preterm infant skin was significantly higher than that obta ined through full-term infant skin which, in turn, was close to that m easured for adult human skin. No significant difference was observed b etween phenobarbital flux values through preterm infant skin and hairl ess mouse skin using flow-through diffusion cells: this result suggest s that hairless mouse skin can be successfully used as a model to stud y in vitro percutaneous absorption of phenobarbital through preterm in fant skin. Phenobarbital flux through preterm infant skin was affected by the gestational age since flux decreased as the gestational age in creased and from 37 weeks gestation onward (full-term infants) flux va lues were similar to those determined for adult human skin. Since by u sing the flux value from the in vitro experiments on preterm infant sk in a steady state plasma concentration close to the therapeutic level can be predicted, phenobarbital transdermal delivery in preterm infant s could be regarded as feasible.