The application of Göttingen minipigs for non-rodent pharmacokinetics (PK) and drug safety testing has seen a dramatic increase in recent years. The aim of this study was to determine the total and unbound brain-to-plasma ratios (K p,brain and K p,uu,brain) for a diverse set of reference compounds in female Göttingen minipigs and compare these with K p,uu,brain values from other species to assess the suitability of Göttingen minipigs as a model for CNS drug safety testing and brain pharmacokinetics (PK) in clinical translation. The reference set consisted of 17 compounds with varying physico-chemical properties and included known human P-glycoprotein (P-gp) substrates. The results of the study showed, that minipig K p,brain and K p,uu,brain values for the tested compounds were in the range 0.03-86 and 0.02-2.4 (n=3-4) respectively. The K p,uu,brain values were comparable between minipig and rat for a large proportion of the compounds (71% within 2-fold, n=17). Comparisons of brain penetration across several species for a subset of reference compounds revealed that minipig values were quite similar to those of rat, dog, monkey and human. The study highlighted that the largest K p,uu,brain species differences were observed for compounds classified as transporter substrates (e.g. cimetidine, risperidone, Way-100635 and altanserin). In conclusion these brain penetration data add substantially to the available literature on PK and drug disposition for minipigs and support use of Göttingen minipig as a non-rodent drug safety model for CNS drug candidates and as a brain PK model for clinical translation.