Induction of Drug Transporters Alters Disposition of Risperidone - A Study in Mice
نویسندگان
چکیده
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.
منابع مشابه
Expression of Drug Pump Protein MRP2 in Lipopolysaccharide-Treated Rats and Its Impact on the Disposition of Acetaminophen
The drug pump protein MRP2 is a membrane drug efflux transporter widely distributed in normal and tumor tissues. Its role is thought to be crucial for the disposition of many drugs and their substrates in different tissues. In this study, we aimed to examine the effects of systematic inflammation induced by lipopolysaccharide (LPS) on the expression and function of this transporter in rats. Jug...
متن کاملExpression of Drug Pump Protein MRP2 in Lipopolysaccharide-Treated Rats and Its Impact on the Disposition of Acetaminophen
The drug pump protein MRP2 is a membrane drug efflux transporter widely distributed in normal and tumor tissues. Its role is thought to be crucial for the disposition of many drugs and their substrates in different tissues. In this study, we aimed to examine the effects of systematic inflammation induced by lipopolysaccharide (LPS) on the expression and function of this transporter in rats. Jug...
متن کاملP-62: Damage to Sperm DNA and Protamine Deficiency Induced by Risperidone in NMRI Mice
Background: Antipsychotic medication use is a common cause of hyperprolactinemia that shown to have adverse effects on male fertility. Risperidone is a combined serotonin/dopamine receptor antagonist that can cause elevations in prolactine level. Its mechanism of cytotoxic effects on testicular germ cells is not fully understood. In the present study we sought to elucidate the impact of risperi...
متن کاملMalaria infection alters the expression of hepatobiliary and placental drug transporters in pregnant mice.
Preventing and treating malaria in pregnancy is a global health priority. However little is known regarding the impact of malaria infection on the maternal and fetal disposition of pharmaceuticals and other xenobiotics. Our objective was to characterize expression of key determinants of drug-disposition in maternal and fetal tissues in a validated murine model of experimental placental malaria....
متن کاملThe role of pregnane X receptor in 2-acetylaminofluorene-mediated induction of drug transport and -metabolizing enzymes in mice.
Activation of the pregnane X receptor (PXR) mediates the induction of several drug transporters and -metabolizing enzymes. In vitro studies have reported that several of these genes are induced after exposure to the hepatocarcinogen, 2-acetylaminofluorene (2-AAF). Thus, we hypothesized that PXR may play a role in the in vivo induction of gene expression by 2-AAF. We examined the expression of t...
متن کامل