Details

Autor(en) / Beteiligte

• Wang, Jun-Sheng
• Ruan, Ying
• Taylor, Robin M.
• Donovan, Jennifer L.
• Markowitz, John S.
• DeVane, C. Lindsay

Titel

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

Ist Teil von

• The international journal of neuropsychopharmacology, 2004-12, Vol.7 (4), p.415-419

Ort / Verlag

Cambridge, UK: Cambridge University Press

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• 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<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.