Modulation of P-glycoprotein transport activity in the mouse blood-brain barrier by rifampin.

In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation.

The ATP-driven drug export pump, P-glycoprotein, is a primary gatekeeper of the blood-brain barrier and a major impediment to central nervous system (CNS) pharmacotherapy. Reducing P-glycoprotein activity dramatically increases penetration of many therapeutic drugs into the CNS. Previous studies in rat showed that brain capillary P-glycoprotein was transcriptionally up-regulated by the pregnane...

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

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-hydroxyris...

Modulation of p-glycoprotein transport function at the blood-brain barrier.

The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to li...

Modulation of P-glycoprotein at the Human Blood-Brain Barrier by Quinidine or Rifampin Treatment: a PET Imaging Study

Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR.

Pharmacotherapy of central nervous system (CNS) disorders is impaired by the drug efflux transporter, P-glycoprotein, which limits drug penetration across the blood-brain barrier into the CNS. One strategy to increase brain drug levels is to modulate P-glycoprotein regulation. This approach requires understanding of the mechanisms that control transporter expression and function. One mechanism ...