Influence of lipophilicity on drug partitioning into sclera, choroid-retinal pigment epithelium, retina, trabecular meshwork, and optic nerve.

The Journal of Pharmacology and Experimental Therapeutics
Rajendra S Kadam, Uday B Kompella

Abstract

In vitro bovine eye tissue/phosphate-buffered saline, pH 7.4, partition coefficients (Kt:b), in vitro binding to natural melanin, and in vivo delivery at 1 h after posterior subconjunctival injection in Brown Norway rats were determined for eight beta-blockers. The Kt:b was in the order intact tissue, dry weight method >or= intact tissue, wet weight method corrected for tissue water and drug in tissue water >> intact tissue, wet weight method > homogenized tissue. In intact tissue methods, Kt:b followed the order choroid-retinal pigment epithelium (RPE) > trabecular meshwork > retina > sclera approximately optic nerve; propranolol > betaxolol > pindolol approximately timolol approximately metoprolol > sotalol approximately atenolol approximately nadolol. Intact tissue, wet weight log (Kt:b) correlated positively with log D for all tissues (R(2) of 0.7-0.9). Log (melanin binding capacity) correlated positively with choroid-RPE log (Kt:b) (R(2) of 0.5). With an increase in concentration, Kt:b decreased in trabecular meshwork for all beta-blockers and for some lipophilic beta-blockers in choroid-RPE and sclera. With an increase in drug lipophilicity, in vivo tissue distribution increased in choroid-RPE, iris-ciliary body, sclera, ...Continue Reading

References

Jan 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·R A FloydJ S Leigh
Oct 1, 1988·Experimental Eye Research·T AbrahamssonG Vauqelin
Mar 15, 1989·Toxicology and Applied Pharmacology·M L GargasM E Andersen
Nov 1, 1983·Journal of Pharmaceutical Sciences·R D Schoenwald, H S Huang
Nov 1, 1982·Biochemical Pharmacology·K B Stepień, T Wilczok
Feb 3, 1999·Regulatory Toxicology and Pharmacology : RTP·B LeblancC Taradach
Sep 3, 2002·Survey of Ophthalmology·David M Maurice
Nov 9, 2004·American Journal of Ophthalmology·Lindsay M SmithenRichard F Spaide
Jan 27, 2005·Investigative Ophthalmology & Visual Science·Leena PitkänenArto Urtti
Apr 14, 2005·Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie·Abdullah Ozkiriş, Kuddusi Erkiliç
Jun 23, 2005·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Neville N OsborneGlyn Chidlow
Nov 22, 2005·Expert Opinion on Drug Delivery·Swita RaghavaUday B Kompella
Dec 31, 2005·Analytical Chemistry·Paweł WiczlingRoman Kaliszan
Mar 23, 2006·Current Opinion in Ophthalmology·Linda M Zangwill, Christopher Bowd
Aug 17, 2006·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Soumyajit MajumdarAshim K Mitra
Sep 28, 2006·Investigative Ophthalmology & Visual Science·Narayan P S Cheruvu, Uday B Kompella
Feb 20, 2007·Molecular Cancer Therapeutics·Nicola F SmithPaul Workman
Oct 24, 2007·Journal of Pharmaceutical Sciences·Joel W Proksch, Keith W Ward
Jan 4, 2008·Investigative Ophthalmology & Visual Science·Aniruddha C AmriteUday B Kompella
Jan 4, 2008·Investigative Ophthalmology & Visual Science·Narayan P S CheruvuUday B Kompella
Apr 26, 2008·Investigative Ophthalmology & Visual Science·Bao Jian FanChi Pui Pang
Jan 2, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Rajendra S Kadam, Uday B Kompella
Mar 21, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Markus FridénMargareta Hammarlund-Udenaes
Apr 23, 2009·Pharmaceutical Research·Eliisa MannermaaArto Urtti
Jun 12, 2009·Investigative Ophthalmology & Visual Science·Chandrasekar DurairajUday B Kompella

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Citations

Jan 11, 2013·JAMA Ophthalmology·Jeremy A LavineNader Sheibani
Aug 25, 2010·Pharmaceutical Research·He WenS Kevin Li
Apr 27, 2010·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Paul MisselNarayan Cheruvu
Apr 20, 2013·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Wennan DuLingyun Cheng
Feb 25, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ashish ThakurUday B Kompella
Nov 24, 2012·Bioanalysis·Y-J XueNaidong Weng
Jul 25, 2012·Therapeutic Delivery·Silvia PescinaSara Nicoli
Jul 17, 2014·Pediatric Research·Letizia PadriniLuca Filippi
Jul 6, 2014·Expert Opinion on Drug Metabolism & Toxicology·Slobodan M Jankovic
Apr 30, 2015·Drug Development and Industrial Pharmacy·He Wen, S Kevin Li
May 15, 2013·Journal of Pharmaceutical Sciences·Lasse MurtomäkiSara Nicoli
Apr 27, 2012·Journal of Pharmaceutical Sciences·Yoshiyuki KuboKen-Ichi Hosoya
Jul 22, 2015·Computer Methods in Biomechanics and Biomedical Engineering·Avinash AyyalasomayajulaJonathan P Vande Geest
Mar 24, 2012·Experimental Eye Research·Chandrasekar DurairajUday B Kompella
Nov 29, 2011·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Jenifer MainsAndrew Urquhart
Nov 15, 2013·Journal of Magnetic Resonance Imaging : JMRI·Yen-Yu I ShihTimothy Q Duong
Mar 27, 2013·Experimental Eye Research·Massimo Dal MontePaola Bagnoli
Mar 15, 2011·Therapeutic Delivery·Uday B KompellaVincent H L Lee
Sep 20, 2005·Experimental Eye Research·Michael R RobinsonKarl G Csaky
Jun 10, 2017·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Ayumi MoriMitsuyoshi Azuma
Dec 3, 2017·Scientific Reports·Rini Rachel JosephSubbu S Venkatraman
Jul 29, 2011·Pharmaceutical Research·Shelley A DurazoUday B Kompella
Jul 25, 2019·Pharmaceutics·Krishna RadhakrishnanSubbu Venkatraman
Feb 4, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Areej QadriKay D Beharry

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