The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein

P-glycoprotein (P-gp) in the brain capillary endothelial cell limits the entry of many drugs into the brain. Our previous in-vitro study using ATPase as a marker of P-gp activity suggested that risperidone might be effectively transported by P-gp. In the present study, we compared the concentrations of risperidone and its major pharmacologically active metabolite 9-hydroxyrisperidone (9-OH-risperidone), in plasma, brain and various other tissues between abcb1ab−/− knockout mice which are functionally devoid of P-gp in their blood–brain barrier vs. FVB wild-type mice. One hour after intraperitoneal injection of 4 μg/g risperidone, the brain concentrations and ratios of brain[ratio ]plasma concentrations of risperidone (13.1-fold and 12-fold respectively, p