Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 7, Issue 4, Pages 415-419Publisher
OXFORD UNIV PRESS
DOI: 10.1017/S1461145704004390
Keywords
P-glycoprotein; 9-OH-risperidone; risperidone
Funding
- NIDA NIH HHS [DA-13027] Funding Source: Medline
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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 mug/g risperidone, the brain concentrations and ratios of brain: plasma concentrations of risperidone (13.1-fold and 12-fold respectively, p < 0.05) and 9-OH-risperidone (29.4-fold and 29-fold respectively, p < 0.01) were significantly higher in the abcb1ab-/- mice than those in the FVB mice. These results indicate that P-gp in the blood-brain barrier significantly influences the brain concentrations of risperidone and 9-OH-risperidone by limiting their CNS access.
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