Bauer Martin, Karch Rudolf, Tournier Nicolas, Cisternino Salvatore, Wadsak Wolfgang, Hacker Marcus, Marhofer Peter, Zeitlinger Markus, Langer Oliver
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
J Nucl Med. 2017 Apr;58(4):678-681. doi: 10.2967/jnumed.116.182147. Epub 2016 Oct 13.
P-glycoprotein (ABCB1) is expressed at the blood-retina barrier (BRB), where it may control distribution of drugs from blood to the retina and thereby influence drug efficacy and toxicity. We performed PET scans with the ABCB1 substrate ()-C-verapamil on 5 healthy male volunteers without and with concurrent infusion of the ABCB1 inhibitor tariquidar. We estimated the rate constants for radiotracer transfer across the BRB (, ) and total retinal distribution volume During ABCB1 inhibition, retinal and influx rate constant were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant was significantly decreased by 2.8 ± 1.0-fold. We found a significant increase in ()-C-verapamil distribution to the retina during ABCB1 inhibition, which provides first in vivo evidence for ABCB1 transport activity at the human BRB. The increase in retinal distribution was approximately 2.5-fold less pronounced than previously reported for the blood-brain barrier.
P-糖蛋白（ABCB1）在血视网膜屏障（BRB）中表达，它可能控制药物从血液到视网膜的分布，从而影响药物疗效和毒性。我们对5名健康男性志愿者进行了PET扫描，使用ABCB1底物（）-C-维拉帕米，分别在未同时输注ABCB1抑制剂他林洛尔和同时输注的情况下进行。我们估计了放射性示踪剂穿过BRB的速率常数（，）和视网膜总分布容积。在ABCB1抑制期间，视网膜和流入速率常数显著增加，分别比基线增加了1.4±0.5倍和1.5±0.3倍。视网膜流出速率常数显著降低了2.8±1.0倍。我们发现，在ABCB1抑制期间，（）-C-维拉帕米在视网膜中的分布显著增加，这为ABCB1在人血视网膜屏障的转运活性提供了首个体内证据。视网膜分布的增加比先前报道的血脑屏障情况大约少2.5倍。
