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Drug Transport Across Blood-Ocular Barriers and Pharmacokinetics

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Pharmacology of Ocular Therapeutics

Abstract

Systemically administered drugs do not reach or have limited diffusion into the eye due to the presence of various ocular barriers. Therefore, intravitreal, intracameral, subconjunctival and sub-tenon routes are the preferred options for directly injecting drugs to into the eyes or ocular structures. Presence of drug transporters in the ocular or retinal barriers play a vital role in the ocular pharmacokinetics of the drugs administered by systemic or direct injection routes. This chapter discusses the involvement of various transporters in providing barrier functions for the transport of drugs in and out of eye. It also discusses about the general principles regarding ocular pharmacokinetics of drugs applied systemically and topically. Studies revealing the functional importance of transporters in barriers and models developed to predict the ocular kinetics of drugs, pharmaceutical factors, ocular drug metabolism and elimination are discussed to give further understanding while selecting a suitable drug for ocular therapy.

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References

  • Adler FH. Textbook of physiology of the eye. St. Louis: CV Mosby; 1962.

    Google Scholar 

  • Alm A, Törnquist P. Lactate transport through the blood-retinal and the blood-brain barrier in rats. Ophthalmic Res. 1985;17(3):181–4.

    Article  CAS  PubMed  Google Scholar 

  • Altenberg GA. Structure of multidrug-resistance proteins of the ATP-binding cassette (ABC) superfamily. Curr Med Chem Anticancer Agents. 2004;4(1):53–62.

    Article  CAS  PubMed  Google Scholar 

  • Anderson JA. Systemic absorption of topical ocularly applied epinephrine and dipivefrin. Arch Ophthalmol. 1980;98(2):350–3.

    Article  CAS  PubMed  Google Scholar 

  • Antoine ME, Edelhauser HF, O'Brien WJ. Pharmacokinetics of topical ocular phenylephrine HCl. Invest Ophthalmol Vis Sci. 1984;25(1):48–54.

    CAS  PubMed  Google Scholar 

  • Asashima T, Hori S, Ohtsuki S, Tachikawa M, Watanabe M, Mukai C, Kitagaki S, Miyakoshi N, Terasaki T. ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells. Pharm Res. 2006;23(6):1235–42.

    Article  CAS  PubMed  Google Scholar 

  • Attar M, Shen J, Ling KH, Tang-Liu D. Ophthalmic drug delivery considerations at the cellular level: drug-metabolising enzymes and transporters. Expert Opin Drug Deliv. 2005;2(5):891–908.

    Article  CAS  PubMed  Google Scholar 

  • Badr GA, Tang J, Ismail-Beigi F, Kern TS. Diabetes downregulates GLUT1 expression in the retina and its microvessels but not in the cerebral cortex or its microvessels. Diabetes. 2000;49(6):1016–21.

    Article  CAS  PubMed  Google Scholar 

  • Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch. 2004;447(5):735–43.

    Article  CAS  PubMed  Google Scholar 

  • Barza M, Baum J, Birkby B, Weinstein L. Intraocular penetration of carbenicillin in the rabbit. Am J Ophthalmol. 1973;75(2):307–13.

    Article  CAS  PubMed  Google Scholar 

  • Barza M, Kane A, Baum J. Pharmacokinetics of intravitreal carbenicillin, cefazolin, and gentamicin in rhesus monkeys. Invest Ophthalmol Vis Sci. 1983;24(12):1602–6.

    CAS  PubMed  Google Scholar 

  • Bito LZ. The physiology and pathophysiology of intraocular fluids. Exp Eye Res. 1977;25(Suppl):273–90.

    Article  CAS  PubMed  Google Scholar 

  • Boulton M, Rózanowska M, Rózanowski B. Retinal photodamage. J Photochem Photobiol B. 2001;64(2–3):144–61.

    Article  CAS  PubMed  Google Scholar 

  • Burnell JM, Kirby WM. Effectiveness of a new compound, benemid, in elevating serum penicillin concentrations. J Clin Invest. 1951;30(7):697–700.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Butler JM, Unger WG, Grierson I. Recent experimental studies on the blood-aqueous barrier: the anatomical basis of the response to injury. Eye (Lond). 1988;2(Suppl):S213–20.

    Article  Google Scholar 

  • Buxton ILO, Benet LZ. Section I, Chapter 2: Pharmacokinetics: the dynamics of drug absorption, distribution, metabolism, and elimination. In: The pharmacological basis of therapeutics. 12th ed. New York: The McGraw-Hill Companies, Inc.; 2011. p. 17–39.

    Google Scholar 

  • Chan-Ling T, Stone J. Degeneration of astrocytes in feline retinopathy of prematurity causes failure of the blood-retinal barrier. Invest Ophthalmol Vis Sci. 1992;33(7):2148–59.

    CAS  PubMed  Google Scholar 

  • Chen MS, Hou PK, Tai TY, Lin BJ. Blood-ocular barriers. Tzu Chi Med J. 2008;20(1):25–34.

    Article  Google Scholar 

  • Chiang CH, Ho JI, Chen JL. Pharmacokinetics and intraocular pressure lowering effect of timolol preparations in rabbit eyes. J Ocul Pharmacol Ther. 1996;12(4):471–80.

    Article  CAS  PubMed  Google Scholar 

  • Chiang CH, Schoenwald RD. Ocular pharmacokinetic models of clonidine-3H hydrochloride. J Pharmacokinet Biopharm. 1986;14(2):175–211.

    Google Scholar 

  • Chowdhury UR, Madden BJ, Charlesworth MC, Fautsch MP. Proteome analysis of human aqueous humor. Invest Ophthalmol Vis Sci. 2010;51(10):4921–31.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cunha-Vaz J. The blood-ocular barriers. Surv Ophthalmol. 1979;23(5):279–96.

    Article  CAS  PubMed  Google Scholar 

  • Cunha-Vaz JG. The blood-ocular barriers: past, present, and future. Doc Ophthalmol. 1997;93(1–2):149–57.

    Article  CAS  PubMed  Google Scholar 

  • Cunha-Vaz JG. The blood-retinal barriers system. Basic concepts and clinical evaluation. Exp Eye Res. 2004;78(3):715–21.

    Article  CAS  PubMed  Google Scholar 

  • Cunha-Vaz J. The blood-retinal barrier in retinal disease. Eur Ophthal Rev. 2009;3(2):105–8.

    Article  Google Scholar 

  • Cunha-Vaz J. Blood-retinal barrier, Encyclopedia of the eye, vol. 1. Oxford: Academic; 2010. p. 209–15.

    Google Scholar 

  • Cunha-Vaz JG, Maurice DM. The active transport of fluorescein by the retinal vessels and the retina. J Physiol. 1967;191(3):467–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11(7):1156–66.

    Article  CAS  PubMed  Google Scholar 

  • Di Marco MP, Chen J, Wainer IW, Ducharme MP. A population pharmacokinetic‐metabolism model for individualizing ciprofloxacin therapy in ophthalmology. Ther Drug Monit. 2004;26(4):401–7.

    Article  PubMed  Google Scholar 

  • Dorrell MI, Aguilar E, Friedlander M. Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion. Invest Ophthalmol Vis Sci. 2002;43(11):3500–10.

    PubMed  Google Scholar 

  • Dorrell MI, Aguilar E, Jacobson R, Trauger SA, Friedlander J, Siuzdak G, Friedlander M. Maintaining retinal astrocytes normalizes revascularization and prevents vascular pathology associated with oxygen-induced retinopathy. Glia. 2010;58(1):43–54.

    Article  PubMed Central  PubMed  Google Scholar 

  • Duvvuri S, Majumdar S, Mitra AK. Role of metabolism in ocular drug delivery. Curr Drug Metab. 2004;5(6):507–15.

    Google Scholar 

  • Eiferman RA, Stagner JI. Intraocular penetration of amikacin. Iris binding and bioavailability. Arch Ophthalmol. 1982;100(11):1817–9.

    Article  CAS  PubMed  Google Scholar 

  • Eljarrat‐Binstock E, Raiskup F, Stepensky D, Domb AJ, Frucht‐Pery J. Delivery of gentamicin to the rabbit eye by drug‐loaded hydrogel iontophoresis. Invest Ophthalmol Vis Sci. 2004;45(8):2543–8.

    Article  PubMed  Google Scholar 

  • Fernandes R, Suzuki K, Kumagai AK. Inner blood-retinal barrier GLUT1 in long-term diabetic rats: an immunogold electron microscopic study. Invest Ophthalmol Vis Sci. 2003;44(7):3150–4.

    Article  PubMed  Google Scholar 

  • Fernandes R, Carvalho AL, Kumagai A, Seica R, Hosoya K, Terasaki T, Murta J, Pereira P, Faro C. Downregulation of retinal GLUT1 in diabetes by ubiquitinylation. Mol Vis. 2004;10:618–28.

    CAS  PubMed  Google Scholar 

  • Fernandes R, Gonçalves A, Cunha-Vaz J. Chapter 6: Blood-retinal barrier: the fundamentals. In: Deepak T, Gerald C, editors. Ocular drug delivery: barriers and application of nanoparticulate systems. Boca Raton: CRC Press/Taylor & Francis; 2012. p. 111–32.

    Chapter  Google Scholar 

  • Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987;84(1):265–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fruttiger M, Calver AR, Kruger WH, Mudhar HS, Michalovich D, Takakura N, Nishikawa S, Richardson WD. PDGF mediates a neuron-astrocyte interaction in the developing retina. Neuron. 1996;17(6):1117–31.

    Article  CAS  PubMed  Google Scholar 

  • Gabelt BT, Kaufman PL. Section 4, Chapter 11: Production and flow of aqueous humor. In: Adler’s physiology of the eye. 11th ed. Edinburgh: Elsevier Inc; 2011. p. 274–307.

    Chapter  Google Scholar 

  • Gao B, Wenzel A, Grimm C, Vavricka SR, Benke D, Meier PJ, Remè CE. Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2002;43(2):510–4.

    PubMed  Google Scholar 

  • Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol. 2002;47 Suppl 2:S253–62.

    Article  PubMed  Google Scholar 

  • Gerhart DZ, Leino RL, Drewes LR. Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina. Neuroscience. 1999;92(1):367–75.

    Article  CAS  PubMed  Google Scholar 

  • Ghiardi GJ, Gidday JM, Roth S. The purine nucleoside adenosine in retinal ischemia-reperfusion injury. Vision Res. 1999;39(15):2519–35.

    Article  CAS  PubMed  Google Scholar 

  • Greenwood J. Characterization of a rat retinal endothelial cell culture and the expression of P-glycoprotein in brain and retinal endothelium in vitro. J Neuroimmunol. 1992;39(1–2):123–32.

    Article  CAS  PubMed  Google Scholar 

  • Gupta SK(1), Velpandian T, Dhingra N, Jaiswal J. Intravitreal pharmacokinetics of plain and liposome-entrapped fluconazole in rabbit eyes. J Ocul Pharmacol Ther. 2000;16(6):511–8.

    Google Scholar 

  • Gunda S, Hariharan S, Mitra AK. Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits. J Ocul Pharmacol Ther. 2006;22(6):465–76.

    Google Scholar 

  • Hagenbuch B, Meier PJ. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta. 2003;1609(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  • Hardberger RE, Hanna C, Goodart R. Effects of drug vehicles on ocular uptake of tetracycline. Am J Ophthalmol. 1975;80(1):133–8.

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Tomi M. Advances in the cell biology of transport via the inner blood-retinal barrier: establishment of cell lines and transport functions. Biol Pharm Bull. 2005;28(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Kondo T, Tomi M, Takanaga H, Ohtsuki S, Terasaki T. MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier: a possible route for delivery of monocarboxylic acid drugs to the retina. Pharm Res. 2001;18(12):1669–76.

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Makihara A, Tsujikawa Y, Yoneyama D, Mori S, Terasaki T, Akanuma S, Tomi M, Tachikawa M. Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine. J Pharmacol Exp Ther. 2009;329(1):87–93.

    Article  CAS  PubMed  Google Scholar 

  • Jordán J, Ruíz-Moreno JM. Advances in the understanding of retinal drug disposition and the role of blood-ocular barrier transporters. Expert Opin Drug Metab Toxicol. 2013;9(9):1181–92.

    PubMed  Google Scholar 

  • Kaur C, Foulds WS, Ling EA. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management. Prog Retin Eye Res. 2008;27(6):622–47.

    Article  CAS  PubMed  Google Scholar 

  • Keren G, Alhalel A, Bartov E, Kitzes-Cohen R, Rubinstein E, Segev S, Treister G. The intravitreal penetration of orally administered ciprofloxacin in humans. Invest Ophthalmol Vis Sci. 1991;32(8):2388–92. PubMed PMID: 2071350.

    Google Scholar 

  • Krishnamurthy P, Schuetz JD. Role of ABCG2/BCRP in biology and medicine. Annu Rev Pharmacol Toxicol. 2006;46:38–410.

    Article  Google Scholar 

  • Lee VHL, Robinson JR. Topical ocular drug delivery: recent developments and future challenges. J Ocul Pharmacol Ther. 1986;2(1):67–108.

    Article  CAS  Google Scholar 

  • Lee VH, Carson LW, Kashi SD, Stratford Jr RE. Metabolic and permeation barriers to the ocular absorption of topically applied enkephalins in albino rabbits. J Ocul Pharmacol. 1986;2(4):345–52.

    Article  CAS  PubMed  Google Scholar 

  • Lutty GA, McLeod DS. Retinal vascular development and oxygen-induced retinopathy: a role for adenosine. Prog Retin Eye Res. 2003;22(1):95–111.

    Article  CAS  PubMed  Google Scholar 

  • Lynch MG, Brown RH, Goode SM, Schoenwald RD, Chien DS. Reduction of phenylephrine drop size in infants achieves equal dilation with decreased systemic absorption. Arch Ophthalmol. 1987;105(10):1364–5.

    Article  CAS  PubMed  Google Scholar 

  • Mannermaa E, Vellonen KS, Urtti A. Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev. 2006;58(11):1136–63.

    Article  CAS  PubMed  Google Scholar 

  • Mayers M, Rush D, Madu A, Motyl M, Miller MH. Pharmacokinetics of amikacin and chloramphenicol in the aqueous humor of rabbits. Antimicrob Agents Chemother. 1991;35(9):1791–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McCarthy TJ. The effect of vehicle composition on the release of chloramphenicol from creams and eye ointments. S Afr Med J. 1975;49(31):1259–62.

    CAS  PubMed  Google Scholar 

  • Miller MH, Madu A, Samathanam G, Rush D, Madu CN, Mathisson K, Mayers M. Fleroxacin pharmacokinetics in aqueous and vitreous humors determined by using complete concentration‐time data from individual rabbits. Antimicrob Agents Chemother. 1992;36(1):32–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Minamizono A, Tomi M, Hosoya K. Inhibition of dehydroascorbic acid transport across the rat blood-retinal and -brain barriers in experimental diabetes. Biol Pharm Bull. 2006;29(10):2148–50.

    Article  CAS  PubMed  Google Scholar 

  • Nagase K, Tomi M, Tachikawa M, Hosoya K. Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. Biochim Biophys Acta. 2006;1758(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  • Nakamura K, Fujiki T, Tamura HO. Age, gender and region-specific differences in drug metabolising enzymes in rat ocular tissues. Exp Eye Res. 2005;81(6):710–5. Epub 2005 Jun 20.

    Article  CAS  PubMed  Google Scholar 

  • Nakashima T, Tomi M, Katayama K, Tachikawa M, Watanabe M, Terasaki T, Hosoya K. Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-retinal barrier. J Neurochem. 2004;89(6):1454–61.

    Article  CAS  PubMed  Google Scholar 

  • Nirmal J, Velpandian T, Biswas NR, Azad RV, Vasantha T, Bhatnagar A, Ghose S. Evaluation of the relevance of OCT blockade on the transcorneal kinetics of topically applied substrates using rabbits FIP 2010 World Congress in Association with AAPS, New Orleans USA. 2010. SA8208/T3427.

    Google Scholar 

  • Nirmal J, Velpandian T, Singh SB, Biswas NR, Azad R, Thavaraj V, Mittal G, Bhatnagar A, Ghose S. Evaluation of the functional importance of organic cation transporters on the ocular disposition of its intravitreally injected substrate in rabbits. Curr Eye Res. 2012;37(12):1127–35. doi: 10.3109/02713683.2012.715715. Epub 2012 Aug 23.

    Google Scholar 

  • Nirmal J, Singh SB, Biswas NR, Thavaraj V, Azad RV, Velpandian T. Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically. Eye (Lond). 2013a;27(10):1196–203.

    Article  CAS  Google Scholar 

  • Nirmal J, Sirohiwal A, Singh SB, Biswas NR, Thavaraj V, Azad RV, Velpandian T. Role of organic cation transporters in the ocular disposition of its intravenously injected substrate in rabbits: implications for ocular drug therapy. Exp Eye Res. 2013b;116:27–35.

    Article  CAS  PubMed  Google Scholar 

  • O’Day DM, Head WS, Robinson RD, Clanton JA. Bioavailability and penetration of topical amphotericin B in the anterior segment of the rabbit eye. J Ocul Pharmacol. 1986;2(4):371–8.

    Article  PubMed  Google Scholar 

  • Occhiutto ML, Freitas FR, Maranhao RC, Costa VP. Breakdown of the blood-ocular barrier as a strategy for the systemic use of nanosystems. Pharmaceutics. 2012;4(2):252–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Oh C, Saville BA, Cheng YL, Rootman DS. Compartmental model for the ocular pharmacokinetics of cyclosporine in rabbits. Pharm Res. 1995;12(3):433–7.

    Article  CAS  PubMed  Google Scholar 

  • Pamulapati CR, Schoenwald RD. Ocular pharmacokinetics of a novel tetrahydroquinoline analog in rabbit: compartmental analysis and PK‐PD evaluation. J Pharm Sci. 2012;101(1):414–23.

    Article  CAS  PubMed  Google Scholar 

  • Patton TF, Robinson JR. Influence of topical anesthesia on tear dynamics and ocular drug bioavailability in albino rabbits. J Pharm Sci. 1975;64(2):267–71.

    Article  CAS  PubMed  Google Scholar 

  • Poitry-Yamate CL, Poitry S, Tsacopoulos M. Lactate released by Müller glial cells is metabolized by photoreceptors from mammalian retina. J Neurosci. 1995;15(7 Pt 2):5179–91.

    CAS  PubMed  Google Scholar 

  • Provis JM, Sandercoe T, Hendrickson AE. Astrocytes and blood vessels define the foveal rim during primate retinal development. Invest Ophthalmol Vis Sci. 2000;41(10):2827–36.

    CAS  PubMed  Google Scholar 

  • Runkle EA, Antonetti DA. The blood-retinal barrier: structure and functional significance. Methods Mol Biol. 2011;686:133–48.

    Article  CAS  PubMed  Google Scholar 

  • Salminen L. Cloxacillin distribution in the rabbit eye after intravenous injection. Acta Ophthalmol. 1978;56(1):11–9.

    Article  CAS  Google Scholar 

  • Sasaki H, Yamamura K, Mukai T, Nishida K, Nakamura J, Nakashima M, Ichikawa M. Pharmacokinetic prediction of the ocular absorption of an instilled drug with ophthalmic viscous vehicle. Biol Pharm Bull. 2000;23(11):1352–6.

    Article  CAS  PubMed  Google Scholar 

  • Schlosshauer B. Chapter 24: Blood–retina barriers. In: Handbook of neurochemistry and molecular neurobiology. New York: Springer US; 2007. p. 486–506.

    Chapter  Google Scholar 

  • Schmitt CJ, Lotti VJ, LeDouarec JC. Penetration of timolol into the rabbit eye. Measurements after ocular instillation and intravenous injection. Arch Ophthalmol. 1980;98(3):547–51.

    Article  CAS  PubMed  Google Scholar 

  • Senthilkumari S, Velpandian T, Biswas NR, Saxena R, Ghose S. Evaluation of the modulation of P-glycoprotein (P-gp) on the intraocular disposition of its substrate in rabbits. Curr Eye Res. 2008a;33(4):333–43.

    Google Scholar 

  • Senthilkumari S, Velpandian T, Biswas NR, Sonali N, Ghose S. Evaluation of the impact of P‐glycoprotein (P‐gp) drug efflux transporter blockade on the systemic and ocular disposition of P‐gp substrate. J Ocul Pharmacol Ther. 2008b;24(3):290–300.

    Google Scholar 

  • Senthilkumari S, Velpandian T, Biswas NR, Bhatnagar A, Mittal G, Ghose S. Evidencing the modulation of P-glycoprotein at blood-ocular barriers using gamma scintigraphy. Curr Eye Res. 2009;34(1):73–7.

    Google Scholar 

  • Senthilkumari S, Lalitha P, Prajna NV, Haripriya A, Nirmal J, Gupta P, Velpandian T. Single and multidose ocular kinetics and stability analysis of extemporaneous formulation of topical voriconazole in humans. Curr Eye Res. 2010;35(11):953–60.

    Article  CAS  PubMed  Google Scholar 

  • Sharma C, Velpandian T, Biswas NR, Nayak N, Vajpayee RB, Ghose S. Development of novel in silico model to predict corneal permeability for congeneric drugs: a QSPR approach. J Biomed Biotechnol. 2011;2011:483869. doi:10.1155/2011/483869. Epub 2011 Feb.

    Article  PubMed Central  PubMed  Google Scholar 

  • Shen J, Cross ST, Tang-Liu DD, Welty DF. Evaluation of an immortalized retinal endothelial cell line as an in vitro model for drug transport studies across the blood-retinal barrier. Pharm Res. 2003;20(9):1357–63.

    Article  CAS  PubMed  Google Scholar 

  • Steinberg RH, Wood I. The relationship of the retinal pigment epithelium to photoreceptor outer segments in human retina. In: Marmor MF, editor. The retinal pigment epithelium. Cambridge/London: Harvard University Press; 1979. p. 32–44.

    Google Scholar 

  • Takata K, Kasahara T, Kasahara M, Ezaki O, Hirano H. Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat. Invest Ophthalmol Vis Sci. 1992;33(2):377–83.

    CAS  PubMed  Google Scholar 

  • Talluri RS, Samanta SK, Gaudana R, Mitra AK. Synthesis, metabolism and cellular permeability of enzymatically stable dipeptide prodrugs of acyclovir. Int J Pharm. 2008;361(1–2):118–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tang-Liu DD, Liu S, Neff J, Sandri R. Disposition of levobunolol after an ophthalmic dose to rabbits. J Pharm Sci. 1987;76(10):780–3.

    Article  CAS  PubMed  Google Scholar 

  • Ueno N, Refojo MF, Liu LH. Pharmacokinetics of the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in the aqueous and vitreous of rabbit. Invest Ophthalmol Vis Sci. 1982;23(2):199–208.

    CAS  PubMed  Google Scholar 

  • Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev. 2006;58(11):1131–5.

    Article  CAS  PubMed  Google Scholar 

  • Velpandian T. Intraocular penetration of antimicrobial agents in ophthalmic infections and drug delivery strategies. Expert Opin Drug Deliv. 2009;6(3):255–70.

    Google Scholar 

  • van Rooyen MM, Coetzee JF, du Toit DF, van Jaarsveld PP. Intraocular concentration time relationships of subconjunctivally administered gentamicin. S Afr Med J. 1991;80(5):236–9.

    PubMed  Google Scholar 

  • Vinores SA. Assessment of blood-retinal barrier integrity. Histol Histopathol. 1995;10(1):141–54.

    CAS  PubMed  Google Scholar 

  • Xuguang S, Yanchuang L, Feng Z, Shiyun L, Xiaotang Y. Pharmacokinetics of chlorhexidine gluconate 0.02% in the rabbit cornea. J Ocul Pharmacol Ther. 2006;22(4):227–30.

    Article  PubMed  Google Scholar 

  • Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD. Transport of antiviral 3′-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol. 2001;18(2):161–7.

    Article  CAS  PubMed  Google Scholar 

  • Zauberman H. Adhesive forces between the retinal pigment epithelium and sensory retina. In: Marmor MF, editor. The retinal pigment epithelium. Cambridge/London: Harvard University Press; 1979. p. 192–204.

    Google Scholar 

  • Zhang Y, Yao Z, Kaila N, Kuebler P, Visich J, Maia M, Tuomi L, Ehrlich JS, Rubio RG, Campochiaro PA. Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema. Ophthalmology. 2014;121(11):2237–46.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, Coimbra University Hospital, Coimbra, Portugal

    Jose Cunha-Vaz MD, PhD, FAAO

  2. Centre for Heath Technology Assessment and Drug Research (CHAD), AIBILI Association for Innovation and Biomedical Research on Light and Image (AIBILI), Azinhaga de Santa Comba, Celas 3000-548, Coimbra, Portugal

    Francisco Batel Marques PhD

  3. Laboratório de Farmacologia e Terapêutica Experimental, IBILI – Faculdade de Medicina da Universidade de Coimbra, Azinhaga de Santa Comba, Celas 3000-548, Coimbra, Portugal

    Rosa Fernandes PhD

  4. School of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, Celas 3000-548, Coimbra, Portugal

    Carlos Alves PhD

  5. Ocular Pharmacology and Pharmacy, Dr. RP Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, 110 029, India

    Thirumurthy Velpandian BPharm, MS(Pharmacol), PhD

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  1. Jose Cunha-Vaz MD, PhD, FAAO
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  5. Thirumurthy Velpandian BPharm, MS(Pharmacol), PhD
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Correspondence to Jose Cunha-Vaz MD, PhD, FAAO .

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  1. Ocular Pharmacology and Pharmacy, Dr. RP Centre for Ophthalmic Sciences, New Delhi, India

    Thirumurthy Velpandian

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Cunha-Vaz, J., Marques, F.B., Fernandes, R., Alves, C., Velpandian, T. (2016). Drug Transport Across Blood-Ocular Barriers and Pharmacokinetics. In: Velpandian, T. (eds) Pharmacology of Ocular Therapeutics. Adis, Cham. https://doi.org/10.1007/978-3-319-25498-2_3

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