Martin Bauer1, Rudolf Karch2, Nicolas Tournier3, Salvatore Cisternino4, Wolfgang Wadsak5, Marcus Hacker5, Peter Marhofer6, Markus Zeitlinger1, Oliver Langer7,5,8. 1. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. 2. Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. 3. Imagerie Moléculaire In Vivo, IMIV, CEA, INSERM, CNRS, Université Paris-Sud, Université Paris Saclay, CEA-SHFJ, Orsay, France. 4. Variabilité de Réponse aux Psychotropes, INSERM, U1144 and Faculté de Pharmacie, Université Paris Descartes, UMR-S 1144, Paris, France. 5. Department of Biomedical Imaging und Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria. 6. Department of Anesthesiology, General Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria; and. 7. Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria oliver.langer@meduniwien.ac.at. 8. Health and Environment Department, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
Abstract
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. Methods: We performed PET scans with the ABCB1 substrate (R)-11C-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 (K1, k2) and total retinal distribution volume VT Results: During ABCB1 inhibition, retinal VT and influx rate constant K1 were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant k2 was significantly decreased by 2.8 ± 1.0-fold. Conclusion: We found a significant increase in (R)-11C-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-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. Methods: We performed PET scans with the ABCB1 substrate (R)-11C-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 (K1, k2) and total retinal distribution volume VT Results: During ABCB1 inhibition, retinal VT and influx rate constant K1 were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant k2 was significantly decreased by 2.8 ± 1.0-fold. Conclusion: We found a significant increase in (R)-11C-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.
Authors: Fernando Caravaggio; Enzo Scifo; Etienne L Sibille; Sergio E Hernandez-Da Mota; Philip Gerretsen; Gary Remington; Ariel Graff-Guerrero Journal: Exp Eye Res Date: 2018-06-05 Impact factor: 3.467
Authors: Andrea Luaces-Rodríguez; Miguel González-Barcia; María José Blanco-Teijeiro; María Gil-Martínez; Francisco Gonzalez; Francisco Gómez-Ulla; María-Jesús Lamas; Francisco-Javier Otero-Espinar; Anxo Fernández-Ferreiro Journal: Pharmaceutics Date: 2018-05-29 Impact factor: 6.321
Authors: Myriam El Biali; Rudolf Karch; Cécile Philippe; Helmuth Haslacher; Nicolas Tournier; Marcus Hacker; Markus Zeitlinger; Doreen Schmidl; Oliver Langer; Martin Bauer Journal: Front Pharmacol Date: 2021-06-16 Impact factor: 5.810