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

Pharmaceutics

David Holthoewer¹  Christoph Hiemke² 

[1] Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Untere Zahlbacher Strasse 8, 55101 Mainz, Germany;

关键词: drug transporter;    P-glycoprotein;    risperidone;    9-hydroxyrisperidone;    antipsychotics;    disposition;   

DOI  :  10.3390/pharmaceutics2020258

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland.