Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier.
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.
Bauer
Martin
M
Department of Clinical Pharmacology, Medical University of Vienna, Vienna 1090, Austria.
Karch
Rudolf
R
Neumann
Friederike
F
Wagner
Claudia C
CC
Kletter
Kurt
K
Müller
Markus
M
Löscher
Wolfgang
W
Zeitlinger
Markus
M
Langer
Oliver
O
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D011804:Quinolines; D014700:Verapamil; C402343:tariquidar