title: Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier.
abstract: We attempted to assess regional differences in cerebral P-glycoprotein (P-gp) function by performing paired positron emission tomography (PET) scans with the P-gp substrate (R)-[(11)C]verapamil in five healthy subjects before and after i.v. infusion of tariquidar (2 mg/kg). Comparison of tariquidar-induced changes in distribution volumes (DVs) in 42 brain regions of interest (ROIs) failed to detect significant differences among brain ROIs. Statistical parametric mapping analysis of parametric DV images visualized symmetrical bilateral clusters with moderately higher DV increases in response to tariquidar administration in cerebellum, parahippocampal gyrus, olfactory gyrus, and middle temporal lobe and cortex, which might reflect moderately decreased P-gp function and expression.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna 1090, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bauer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Karch
authors.forename: Friederike
authors.initials: F
authors.lastname: Neumann
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Wagner
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000328:Adult; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging; D002121:Calcium Channel Blockers / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008297:Male; D049268:Positron-Emission Tomography; D011804:Quinolines / Q000494:pharmacology*; D014700:Verapamil / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D011804:Quinolines; D014700:Verapamil; C402343:tariquidar