The primary metabolites of PG were measured in dog and human plasma following oral administration of enteric coated MEDI7219 tablets to examine a potential mechanism of the PG- mediated renal toxicity in dog and its possible translatability to humans. Plasma concentrations of PG, its phase-I metabolites GA and 4OMGA and phase-II glucuronide and glutathione conjugates were measured. The human and dog samples, collected through 8 hours after administration, were analyzed and the results were compared (Figure ). Based on allometric scaling method the highest daily dose administered in humans was approximately 8-fold less compared with the dose level tested in dogs. However, at these doses the observed exposures to PG, GA or 4OMGA were comparable between the two species, thus suggesting that humans may have greater oral bioavailability of PG than dogs. However, as to our knowledge PG exposure data following IV administration is not available for either humans or dogs and therefore a potential species difference in PG bioavailability cannot be confirmed. The metabolism pattern between the two species was largely similar with some differences observed in exposure of PG glucuronides and GA glucuronides. PG glucuronides had higher exposure while GA-3-glucoronides showed lower exposure in humans than in dogs. Both PG-GSH and GA-GSH conjugates had very low exposure in circulation with potential minor differences between humans and dog observed.