title: Induction of Drug Transporters Alters Disposition of Risperidone - A Study in Mice.
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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Untere Zahlbacher Strasse 8, 55101 Mainz, Germany. holthoewer@psychiatrie.klinik.uni-mainz.de.
authors.forename: David
authors.initials: D
authors.lastname: Holthoewer
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Untere Zahlbacher Strasse 8, 55101 Mainz, Germany. hiemke@uni-mainz.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Untere Zahlbacher Strasse 8, 55101 Mainz, Germany. schmitt@psychiatrie.klinik.uni-mainz.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schmitt
keywords: 9-hydroxyrisperidone; P-glycoprotein; antipsychotics; disposition; drug transporter; risperidone