The anti-Parkinson drug budipine is exported actively out of the brain by P-glycoprotein in mice

P-glycoprotein, a product of the ABCB1 gene, is a plasma membrane transporter that exports certain drugs as well as endogenous substances against a concentration gradient in the intestines, kidney and testes. It also constitutes an important part of the blood-brain barrier, where it exports its substrates out of the brain back into the circulation. To investigate whether the uptake of the anti-Parkinson drug budipine into the brain is mediated by P-glycoprotein, abeblab(-/-) double knock-out mice and wild-type control mice received budipine continuously over 11 days via implanted osmotic infusion pumps at the rate of 30 ug over 24h. Concentrations of the drug in plasma, brain, and organs were measured with HPLC. Budipine concentrations in the abcb1ab knock-out animals were 3.1 times higher than in control mice. This study confirms the important role P-gp plays at the blood-brain barrier and shows that budipine is a substrate of P-gp. (c) 2005 Elsevier Ireland Ltd. All rights reserved.