The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein.
The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein.
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DOI：
10.1017/s1461145704004390
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发表时间：
2004-12
期刊：
影响因子：
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通讯作者：
Jun-sheng Wang;Y. Ruan;Robin M. Taylor;J. Donovan;John S. Markowitz;C. DeVane
中科院分区：
文献类型：
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作者：
Jun-sheng Wang;Y. Ruan;Robin M. Taylor;J. Donovan;John S. Markowitz;C. DeVane
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 microg/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.
