caa a22 4500 477125573 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970101xx s 000 0 eng 10.1023/A:1012011618785 doi (NATIONALLICENCE)springer-10.1023/A:1012011618785 Intravenous Infusion of RMP-7 Increases Ocular Uptake of Ganciclovir [Elektronische Daten] [Peter Elliot, Raymond Bartus, Jasmina Mackic, Berislav Zlokovic] Purpose. The ability of intravenous (i.v.) infusions of the bradykinin agonist, RMP-7, to permeabilize the blood-ocular barriers (BOB) to the antiviral agent ganciclovir was investigated in guinea-pigs. Methods. Different i.v. dosing regimens included pre-treatment with RMP-7 (0.2 μg/kg/min for 5 min) followed by either [3H]-ganciclovir (1 μCi/0.2 ml/min) alone, and/or co-infusion with RMP-7 and [3H]-ganciclovir. At specific times the animals were sacrificed, their eyes removed, and the retina and lens epithelium dissected and analyzed for the amount of radioactivity. Results. Using the ratio of tissue vs. integrated plasma radioactivity concentration, a two-fold increase in ganciclovir steady-state levels were observed in the retina as well as lens epithelium following RMP-7 pretreatment. Peak uptake effects were achieved with a 4.5 min ganciclovir infusion. Neither longer infusions of ganciclovir alone, nor co-infusions of RMP-7 and ganciclovir further enhanced the uptake effects. Kinetic analysis indicated that RMP-7 increased the rate of ganciclovir entry (K IN) in studied ocular tissues, while the efflux of drug (K OUT) was not affected by this treatment. Finally, ganciclovir retina:plasma ratios elevated by RMP-7 pre-treatment, remained higher than control ratios within 60 min following cessation of 4.5 min ganciclovir infusion. Conclusions. These data offer further evidence that BOB and in particular the blood-retinal barrier can be permeabilized via bradykinin receptor stimulation. As the i.v. infusions of RMP-7 enhanced the retinal uptake of ganciclovir, it is suggested that a combination of RMP-7 and ganciclovir may provide a novel approach for treating cytomegalo-virus retinis. Plenum Publishing Corporation, 1997 blood-ocular barriers nationallicence bradykinin nationallicence drug delivery nationallicence retina nationallicence guinea pig nationallicence Elliot Peter Alkermes Inc., 02139, Cambridge, Massachusetts aut Bartus Raymond Alkermes Inc., 02139, Cambridge, Massachusetts aut Mackic Jasmina Department of Neurological Surgery, University of Southern California, School of Medicine, 2025 Zonal Avenue, Raulston Memorial Building 506, 90033, Los Angeles, California aut Zlokovic Berislav Department of Neurological Surgery, University of Southern California, School of Medicine, 2025 Zonal Avenue, Raulston Memorial Building 506, 90033, Los Angeles, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 80-85 0724-8741 14:1<80 1997 14 11095 https://doi.org/10.1023/A:1012011618785 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012011618785 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Elliot Peter Alkermes Inc., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Bartus Raymond Alkermes Inc., 02139, Cambridge, Massachusetts aut NATIONALLICENCE 700 1- Mackic Jasmina Department of Neurological Surgery, University of Southern California, School of Medicine, 2025 Zonal Avenue, Raulston Memorial Building 506, 90033, Los Angeles, California aut NATIONALLICENCE 700 1- Zlokovic Berislav Department of Neurological Surgery, University of Southern California, School of Medicine, 2025 Zonal Avenue, Raulston Memorial Building 506, 90033, Los Angeles, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 80-85 0724-8741 14:1<80 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer