PMID: 11905988Mar 22, 2002Paper

The distribution of the anti-HIV drug, 2'3'-dideoxycytidine (ddC), across the blood-brain and blood-cerebrospinal fluid barriers and the influence of organic anion transport inhibitors

Journal of Neurochemistry
J E Gibbs, S A Thomas

Abstract

The brain and CSF distribution of the HIV reverse transcriptase inhibitor, 2'3'-dideoxycytidine (ddC), was investigated by the in situ brain perfusion and isolated incubated choroid plexus methods in the guinea pig. Multiple-time brain perfusions indicated that the distribution of [3H]ddC to the brain and CSF was low and the unidirectional rate constant (K(in)) for the brain uptake of this nucleoside analogue (0.52 +/- 0.10 microL/min/g) was not significantly different to that for the vascular marker, [14C]mannitol (0.44 +/- 0.09 microL/min/g). The influence of unlabelled ddC, six organic anion transport inhibitors and 3'-azido 3'-deoxythymidine (AZT) on the CNS uptake of [3H]ddC was examined in situ and in vitro. ddC, probenecid and 2,4-dichlorophenoxyacetic acid altered the distribution of [3H]ddC into the brain and choroid plexuses, indicating that the limited distribution of [3H]ddC was a result of an organic anion efflux transporter, in addition to the low lipophilicity of this drug (octanol-saline partition coefficient, 0.047 +/- 0.001). The CNS distribution was also sensitive to p-aminohippurate and deltorphin II, but not digoxin, suggesting the involvement of organic anion transporters (OAT1/OAT3-like) and organic anion...Continue Reading

Citations

Aug 24, 2011·Cancer Chemotherapy and Pharmacology·Denise Campos-ArroyoJorge Melendez-Zajgla
Jul 20, 2005·Pharmaceutical Research·Conrad E JohansonAndrew Baird
Jan 30, 2004·Psychoneuroendocrinology·Carmine M ParianteRobert W Kerwin
Jan 22, 2003·Advanced Drug Delivery Reviews·Haiying SunWilliam F Elmquist
Mar 7, 2012·ACS Chemical Biology·Edward A MoteaAnthony J Berdis
Dec 21, 2005·Acta Pharmacologica Sinica·Yo-han Oh, Hyo-kyung Han
Nov 9, 2010·The Journal of Pharmacology and Experimental Therapeutics·Sinthujah JeganathanSarah A Thomas
Jan 5, 2006·Cerebrospinal Fluid Research·Christy AnthonypillaiSarah A Thomas
Dec 9, 2004·Pharmacotherapy·Anthony J BustiDavid M Margolis
Aug 2, 2006·HIV Clinical Trials·Bryan McGeeFrancesca Aweeka
Jun 6, 2008·Journal of Clinical Pharmacology·Craig R RaynerE Niclas Jonsson
Jul 11, 2007·Journal of Pharmaceutical Sciences·Ivan O EdafioghoK R Scott
Mar 7, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Tao ZhouRobert C Hider
May 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·J E GibbsS A Thomas
Apr 8, 2004·American Journal of Physiology. Renal Physiology·Geri L Youngblood, Douglas H Sweet
Feb 24, 2011·Metallomics : Integrated Biometal Science·Robert C HiderJane Preston
Jun 21, 2017·Neurochemical Research·Jianyi NiuZhaohui Zhang
Jan 21, 2006·The Journal of Pharmacology and Experimental Therapeutics·J E GibbsS A Thomas
Nov 17, 2004·Reviews in Medical Virology·Nathalie Strazielle, Jean-François Ghersi-Egea
Nov 25, 2003·The Journal of Pharmacology and Experimental Therapeutics·C AnthonypillaiS A Thomas
Apr 18, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Guoyu PanWilliam F Elmquist
Feb 13, 2003·Brain Pathology·Apsara KandanearatchiIan Paul Everall
Oct 23, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Supratim ChoudhuriCurtis D Klaassen
Aug 6, 2011·Pharmacology & Therapeutics·Gerard MinuesaJavier Martinez-Picado

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