Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study

被引：74

作者：

Bauer, Martin ^{[1
]}

Karch, Rudolf ^{[2
]}

Zeitlinger, Markus ^{[1
]}

Philippe, Cecile ^{[3
]}

Roemermann, Kerstin ^{[1
,4
]}

Stanek, Johann ^{[1
,5
]}

Maier-Salamon, Alexandra ^{[6
]}

Wadsak, Wolfgang ^{[3
,7
]}

Jaeger, Walter ^{[6
]}

Hacker, Marcus ^{[3
,7
]}

Mueller, Markus ^{[1
]}

Langer, Oliver ^{[1
,5
,7
]}

机构：

[1] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria

[2] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, A-1090 Vienna, Austria

[3] Med Univ Vienna, Div Nucl Med, Dept Biomed Imaging & Image Guided Therapy, A-1090 Vienna, Austria

[4] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Ctr Syst Neurosci, Hannover, Germany

[5] AIT Austrian Inst Technol GmbH, Hlth & Environm Dept, Seibersdorf, Austria

[6] Univ Vienna, Dept Clin Pharm & Diagnost, Vienna, Austria

[7] Med Univ Vienna, Med Imaging Cluster, A-1090 Vienna, Austria

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2015年 / 35卷 / 05期

基金：

奥地利科学基金会;

关键词：

blood-brain barrier; P-glycoprotein; pituitary gland; positron emission tomography; (R)-[C-11]verapamil; tariquidar; POSITRON-EMISSION-TOMOGRAPHY; DRUG-DRUG INTERACTIONS; C-11-VERAPAMIL; FLOW;

D O I：

10.1038/jcbfm.2015.19

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

As P-glycoprotein (Pgp) inhibition at the blood-brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[C-11] verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (V-T) of (R)-[C-11] verapamil in whole-brain gray matter increased by 273 +/- 78% relative to baseline scans without tariquidar, which was higher than previously reported V-T increases. During tariquidar infusion whole-brain V-T was comparable to V-T in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.

引用

页码：743 / 746

页数：4

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