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Pharmaceutics 2010, 2(2), 258-274; doi:10.3390/pharmaceutics2020258

Induction of Drug Transporters Alters Disposition of Risperidone - A Study in Mice

Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Untere Zahlbacher Strasse 8, 55101 Mainz, Germany
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Received: 24 May 2010 / Accepted: 1 June 2010 / Published: 2 June 2010
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Abstract

Pharmacokinetic interactions, e.g. modulation of drug transporters like P-glycoprotein at the blood-brain barrier, can be a reason for treatment non-response. This study focuses on the influence of induction of drug transporters on the disposition of the antipsychotic drugs risperidone and 9-hydroxyrisperidone. Brain and serum concentrations of risperidone and its active metabolite 9-hydroxyrisperidone, which are known P-glycoprotein substrates, were measured after drug transporter induction with rifampicin, dexamethasone or 5-pregnene-3beta-ol-20-on-16alpha-carbonitrile using high performance liquid chromatography. Disposition of risperidone and 9-hydroxyrisperidone was dramatically decreased in mouse brain and serum after drug transporter induction. The metabolism of risperidone was also affected.
Keywords: drug transporter; P-glycoprotein; risperidone; 9-hydroxyrisperidone; antipsychotics; disposition drug transporter; P-glycoprotein; risperidone; 9-hydroxyrisperidone; antipsychotics; disposition
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Holthoewer, D.; Hiemke, C.; Schmitt, U. Induction of Drug Transporters Alters Disposition of Risperidone - A Study in Mice. Pharmaceutics 2010, 2, 258-274.

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