“…P-gp is highly expressed in brain capillary endothelial cells and functions as a protective efflux transporter, ejecting molecules back out into the blood plasma, restricting their passage into the brain parenchyma [4,5]. These complex properties make phenytoin a very interesting model drug for pharmaceutical studies, as evidenced by a large number of studies available in the literature, covering a range of fields including formulation science [6,7], pharmacokinetic characterization [8,9], and pharmacodynamic investigations in seizure models [10,11]. Given the complexity of phenytoin pharmacokinetics, simultaneous investigation of the concentrations of its major metabolite 4-HPPH, although not always studied, may yield important supplementary information on its distribution and metabolism in the body, especially with respect to the in vivo evaluation of novel targeted drug delivery systems, a field which is rapidly advancing in pharmaceutical science.…”